LIST OF CONTENTS - Welcome to...

M/s. Symed Labs Ltd. Unit - VI

Prepared By Rightsource Industrial Solutions Pvt. Ltd.

LIST OF CONTENTS

S. No Content Annexure Page No Enclosures

1 CFE Copy

Enclosed

2 CFO Copy

3 NOC from Grampanchayath

4 Land Documents

Annexures

1 List of Products Annexure-I 1

2 Site Plan Annexure-II 2 3 Manufaturing Process Description Annexure-III 3-131 4 Water Consumption Details Annexure-IV 132 5 Waste water Details Annexure-V 133

6 Hazardous waste Annexure-VI

134 7 Industrial Process waste 8 Sewage sludge 9 Solid waste 10 Stack Emission Details Annexure- VII 135-136 11 Process Emission Details Annexure-VIII 137 12 List of Raw Materials Annexure-IX 138-165 13 Solvent Details Annexure-X 166-170

COPY OF CFE

COPY OF CFO

NOC FROM GRAMPANCHAYATH

LAND DOCUMENT

ADDITIONAL INFORMATION

Additional Information M/s. Symed Labs Ltd. Unit - VI

Prepared By Rightsource Industrial Solutions Pvt. Ltd. Page 1

Annexure - I LIST OF PROPOSED PRODUCTS

S.No Product Name CAS Number Therapeutic category

Production Capacity

Kgs/Month

Production Capacity Kgs/Day

1 Amisulpride 71675-85-9 Neuroleptic agent 3000.00 100.00 2 Carvedilol 72956-09-3 Cardiovascular Agent 60000.00 2000.00 3 Carvedilol Phosphate 610309-89-2 Antihypertensive agent 7600.00 253.33 4 Carbidopa 93357-67-6 Anti parkinsonian agent 6000.00 200.00

5 Cinitapride Hydrogen tartarate 66564-14-5 Gastroprokinetic Agent 6300.00 210.00

6 Dapoxetine Hydrochloride

129938-20-1 Antidepressant 3000.00 100.00

7 Epalrestat 82159-09-9 oral antidiabetic agent 9000.00 300.00 8 Eszopiclone 138729-47-2 Nonbarbiturate Hypnotic 150.00 5.00 9 Fluconazole 86386-73-4 Antifungal 18000.00 600.00 10 Iron sucrose 8047-67-4 Iron supplement 20000.00 666.67 11 Itopride Hydrochloride 122892-31-3 Antiulcer 12000.00 400.00 12 ketorolac tromethamine 74103-07-4 Antipyretic agent 24000.00 800.00 13 Levocetirizine DiHCl 130018-87-0 Antihistamine agent 1800.00 60.00

14 Levosulpride 23672-07-3 Antiemetic agent 39000.00 1300.00

15 Linezolid 165800-03-3 Antibiotic 70000.00 2333.33

16 Mosapride Citrate Dihydrate 63582-62-2 Gastroprokinetic 12000.00 400.00

17 Ondansetron Hydrochloride Dihydrate 103639-04-9 Antiemetic 3000.00 100.00

18 Pregabalin 148553-50-8 Neuropathic Pain Agent 20000.00 666.67 19 Racecadotril 81110-73-8 Anti diarrheal 8000.00 266.67 20 Tamsulosin HCl 106463-17-6 Anti-adrenergic 10300.00 343.33 21 Tizanidine HCl 64461-82-1 Skeletal muscle relaxant 300.00 10.00 22 Topiramate 97240-79-4 Anticonvulsant 3000.00 100.00 23 Zotepine 43200-80-2 Nonbarbiturate Hypnotic 6000.00 200.00

24 Zopiclone 26615-21-4 Neuroleptic agent 10300.00 343.33

25 Deferasirox 201530-41-8 Chelating Agent

7000.00 233.33

26 Tapentadol Hydrochloride 175591-09-0 Analgesic 20000.00 666.67

27 Thalidomide 50-35-1 Immuno modulator, angiogenesis inhibitor 8250.00 275.00

28 Tofisopam 22345-47-7 Anxiolytic agent 12000.00 400.00

Total 400000.00 13333.33



SITE LAYOUT Annexure-II



MANUFACTURING PROCESS DESCRIPTION

Annexure-III

1. AMISULPRIDE

Process Description:

Stage-1

4-Amino-5-(ethyl sulfonyl)-2-methoxybenzoic acid reacts with 1-(1-ethylpyrrolidin-2-

yl) methane amine in the presence of ethyl chloro formate, Triethyl amine in acetone,

Sodium hydroxide and water to yield Amisulpride (crude).

Stage-2

Amisulpride(Crude) is recrystallised from isopropyl alcohol and carbon to yield

Amisulpride(pharma).



AMISULPRIDE

Route of Synthesis:

Stage-1:

S

H2N OCH3

OH

O

H3C

O O

4-Amino-5-ethanesulfonyl-2-methoxy-benzoic acid

C10H13NO5S

259.28

+N

H2N

H3C

C-(1-Ethyl-pyrrolidin-2-yl)-methylamine

C7H16N2

128.22

+ (C2H5)3N

Triethyl amine

101.19

+ ClCOOC2H5

Ethyl chloro formate

108.52

MDC

S

H2N OCH3

NH

O

H3CO O

N

H3C

Amisulpride (Crude)

C17H27N3O4S

369.48

+ (C2H5)3N.HCl

Triethyl amine hydrochloride

137.65

+ C2H5OH

46.07

+ CO2

44.0



Stage-2:

S

H2N OCH3

NH

OH3C

O ON

H3C

Amisulpride(Crude)

C17H27N3O4S

369.48

S

H2N OCH3

NH

OH3C

O O

N

H3C

Amisulpride(pure)

C17H27N3O4S

369.48



AMISULPRIDE

Flow Chart:

Stage-1

4-Amino-5-(ethylsulfonyl)-2-methoxy benzoic acid1-(1-ethylpyrrolidin-2-yl)methanamineEthyl chloro formateAcetone

Acetone Rec

AMISULPRIDE

Stage-2Stage-1IPA

IPA Rec



AMISULPRIDE

Material Balance:

Material Balance of Amisulpride Stage-1

Batch Size: 200.0Kg Name of the input Quantity

in Kg Name of the out put Quantity

in Kg 2-Methoxy-4-amino-5-ethyl sulphonyl benzoic acid

141.00 Stage-1 200.00

1-Ethyl-2-amino methyl pyrrolidine

75.00 Acetone Recovery 588.00

Ethyl chloro formate 59.00 Acetone Loss 31.00 Triethylamine 80.00 Effluent water 1445.83 Sodium hydroxide 145.00 (Water-1200,Triethylamine HCl-

74.83,Ethanol-25.0,Sodium hydroxide-145,Aetone-1)

Acetone 630.00 Process Emissions 23.92 Water 1200.00 (Carbon dioxide-23.92) Organic Residue 41.25 (Organic impurities-31.25,

Acetone-10)

Total 2330.00 Total 2330.00

Material Balance of Amisulpride Stage-2



in Kg Stage-1 200.00 Amisulpride(Pharma) 200.00 Isopropyl alcohol 150.00 Isopropyl alcohol Recovery 143.00 Activated carbon 9.00 Isopropyl alcohol Loss 7.00 Spent carbon 9.00 Total 359.00 Total 359.00



2. CARVEDILOL


4-Oxiranylmethoxy-9H-Carbazole is condensed with 2-(2-methoxyphenoxy)

ethylamine in the presence of Ethyl acetate to give Carvedilol as product.



CARVEDILOL

Route of synthesis:

Stage-1

4-(oxiranylmethoxy)-9H-Carbazole

NH

O

O

C15H13NO2

239.27

+

2-(2-methoxyphenoxy)ethylamine

NH2

OO

C9H13NO2

167.21

Ethyl acetate

NH

O NH

OH

O

H3CO

Carvedilol

C24H28N2O4

406.47



CARVEDILOL

Flow Chart:

4(Oxiranyl methoxy)-9H-Carbazole(2-methoxyphenoxy)ethylamineEthyl acetateMethanol

Stage-1 Ethyl acetate RecMethanol Rec

CARVEDILOL



CARVEDILOL

Material Balance:

Material balance of Carvedilol Stage-1

Batch Size:55.0 Kg Name of the input Quantity


In Kg 4(Oxiranyl methoxy)-9H-Carbazole

45.00 Carvedilol 55.00

(2-methoxyphenoxy)ethylamine 35.00 Ethyl acetate Recovery 393.00 Ethyl acetate 438.00 Ethyl acetate Loss 20.00 Methanol 420.00 Methanol Recovery 376.00 Methanol Loss 19.00 Ethyl acetate + Methanol

Recovery 49.50

Spent Carbon 2.00 Organic residue 23.50 (Organic Impurities-23.5) Total 938.00 Total 938.00



3. CARVEDILOL PHOPSHATE


Stage-1

Carvedilol reacts with Phosphoric acid in the presence of Acetone and water media

to give Carvedilol phosphate as product.



CARVEDILOL PHOPSHATE

Route of Synthesis:

Stage-1

NH

O

OH

NH

O

H3CO

Carvedilol

C24H26N2O4

406.47

+ H3PO4

Phosphoric acid

98.0

Acetone

NH

O

OH

NH

O

H3CO P

O

HO

OH

OH

Carvedilol Phosphate

C24H29N2PO8

504.47




Flow Chart:

CarvedilolPhopshoric acidAcetone

Stage-1 Acetone Rec

CARVEDILOL PHOSPHATE




Material Balance:

Material balance of Carvedilol Phopshate Stage-1



In Kg Carvedilol 47.00 Carvedilol Phopshate 58.00 Phosphoric acid 12.00 Acetone Recovery 370.00 Acetone 396.00 Acetone Loss 19.00 Water 50.00 Effluent water 51.50 (Water-50,Acetone-1,phosphoric

acid-0.5)

Organic Residue 6.50 (Organic Impurities-0.5,Acetone-

6)

Total 505.00 Total 505.00



4. CARBIDOPA


Stage-1

Methyldopa is reacted with Thionyl Chloride in presence of Methanol to obtain

Methyldopa Methyl Ester

Stage-2

Toluene, Cyclohexanone, Purified water and Liq. Ammonia are charged into reactor

and sodium hypochlorite solution is added. After competition of reaction, organic

layer is separated and washed with Dil. Hydrochloric acid and purified water. The

obtained organic layer and Boric acid is reacted with Carbidopa Stage-1. Obtained

Organic layer is extracted into aqueous layer and further washings with chloroform

then Stage-2 will be obtained

Stage-3

The Stage-2 Aqueous layer is refluxed for 8-10 hours. Cooled, then methanol was

added to it and further PH adjusted to 3.0-3.5 with Ammonia and cool the mass to

isolate stage-3 by centrifugation.

Stage-4

Crude carbidopa was dissolved in dilute hydrochloric acid and treated with activated

carbon and sodium metabisulphite. To filtered solution methanol was added and PH

was adjusted to 3.0-3.5 and filtered to get Carbidopa and further purified with

Hydrochloric acid, water and sodium meta bisulphate.



CARBIDOPA

Route of Synthesis:

Stage-1:

Methyl Dopa

HO

HO

NH2

OH

OH3C

+ SOCl2 + CH3OH

HO

HO

NH2

O

OH3C

C10H13NO4

211.21

Thionyl Chloride Methanol

Methyl Dopa Methyl Ester

C11H15NO4

225.24

+ SO2+

+ 2 NaOH

Sodium Hydroxide

118.97 32.0 2X40.0=80.0

2NaCl + 2H2O

Sodium Chloride Water Sulphur dioxide

2X58.5=117 2X18.0=36.0 64.0

Stage-2:

Cyclohexanone

O

C6H10O

98.11

+ NaOCl + NH3

3 3-pentamethylene oxaziridine

O NH

C6H11NO

113.16

+ NaCl + H2O

74.44 17.0 58.5 18.0



Stage-3:

Step-A

HO

HO

NH2

O

OH3C

Methyl Dopa Methyl Ester

C11H15NO4

225.24

HO

HO

NH

O

OH3C

N

+

3 3-pentamethylene oxaziridine

O NH

C6H11NO

113.16

(s)-2-Cyclohexylidene-Hydrazino-2-(3,4-Dihydroxybenzyl)-Propionic acid

methyl ester

C17H24N2O4

320.38

+ H2O

18.0

Boric Acid



Step-B

HO

HO

NH

O

OH3C

N

(s)-2-Cyclohexylidene-Hydrazino-2-(3,4-Dihydroxybenzyl)-Propionic acid

methyl ester

C17H24N2O4

320.38

HO

HO

NH

O

OH3C

NH2

Carbidopa Methyl Ester

C11H16N2O4

240.26

O

Cyclohexane

C6H10O

98.14

+ NH3 + HCl

17.0 36.5

H2O

+

+

18.0

+ NH4Cl

Ammonium Chloride

53.5

Methanol



Stage-4:

HO

HO

NH

O

OH3C

NH2

Carbidopa Methyl Ester

C11H16N2O4

240.26

+ H2O + HCl + NH4OH

18.0 36.5 35.0

HO

HO

OH

OH3C

NH

NH2

H2O

+ CH3OH + NH4Cl

Carbidopa

C10H14N2O4 H2O

244.24

32.0 53.5

Methanol



CARBIDOPA

Flow Chart:

Stage-1

Stage-2 Effluent Water

Stage-3

Stage-4

Carbidopa

Methyl DopaMethanolThionyl ChlorideCaustic Soda FlakesWater

Methanol RecoverySulphurdioxide

CyclohexanoneTolueneLiquid AmmoniaSodium Hypochlorite solutionConc. Hydrochloric AcidWater

Stage-1Stage-2 in TolueneBoric AcidConc. Hydrochloric AcidChloroformMethanolLiq.AmmoniaSodium metabisulphite

Toluene RecoveryChloroform RecoveryMethanol Recovery

Hydrochloric AcidMethanolLiquid AmmoniaSodium meta bisulphateAcetoneActivated Carbon

Methanol ChlorideAmmonium ChlorideSpent Carbon



CARBIDOPA

Material Balance:

Material balance of Carbidopa Stage-1



In Kg Methyl Dopa 40.00 Stage-1 40.00 Methanol 100.00 Methanol Recovery 85.00 Thionyl Chloride 22.53 Methanol Loss 5.00 Caustic Soda Flakes 15.50 Effluent Water 387.91 Water 355.00 (Water-355,generated water-

6.82,Sodium Chloride-22.15, Methanol-3.94)

Process Emission 12.12 (Sulfur dioxide) Total 533.03 Total 530.03




In Kg Cyclohexanone 20.00 Stage-2 in Toluene 340.00 Toluene 320.00 Effluent Water 215.47 Liquid Ammonia 3.50 (Water-200,generated water-

3.67,Sodium chloride-11.8)

Sodium Hypochlorite 15.00 Organic Residue 33.03 Conc. Hydrochloric Acid 30.00 Water 200.00 Total 588.50 Total 588.50






In Kg Stage-1 40.00 Stage-3 35.00 Stage-2 in Toluene 340.00 Toluene Recovery 299.00 Boric Acid 7.25 Toluene Loss 16.00 Conc. Hydrochloric Acid 12.00 Chloroform Recovery 178.00 Chloroform 187.50 Chloroform Loss 9.50 Methanol 20.00 Cyclohexanone Recovery 14.30 Liq.Ammonia 7.00 Effluent Water 147.28 Sodium meta bisulphite 0.55 (Water-97.3,generated water-

3.18,Methanol-20,Boric Acid-7.25,Ammonium chloride-19,Sodium metabisulphite-0.55)

Water 100.00 Organic Residue 15.22 (Organic impurities-10.22,

Toluene-5)





In Kg Stage-3 35.00 Carbidopa 25.00 Hydrochloric Acid 7.00 Methanol Recovery 170.00 Methanol 182.35 Methanol Loss 5.00 Ammonium hydroxide 5.00 Effluent Water 62.22 Sodium meta bisulphate 0.87 (Water-47.40, Methanol-4.67,

Acetone-1.64, Ammonium Chloride-7.64,Sodium meta bisulphate-0.87)

Acetone 1.64 Spent Carbon 5.00 Activated Carbon 5.00 Organic Residue 19.64 Water 50.00 (Organic Impurities-

14.64,Methanol-5)




5. CINITAPRIDE HYDROGEN TARTRATE


Stage-1

3-Cyclohexane-1-methanol reacts with Benzenesulfonyl chloride,4-Amino-2-ethoxy-

5-nitro-N-(4-piperidyl)benzamide in presence of Cyclohexane and Methanol as a

solvent media to give Cinitapride Hydrogen Tartrate



CINITAPRIDE HYDROGEN TARTRATE

Route of Synthesis

Stage-1

OH

Cyclohex-3-enyl-methanolC7H12O

112.17

+

Benzene sulfonyl chloride

SOO

Cl

C6H5ClO2S

176.62

NO2

H2N

O O

HN

NH

CH3

4-Amino-2-ethoxy-5-nitro-N-piperidin-4-yl-benzamide

C14H20N4O4

308.33

++

1/2 Na2CO3

Sodium carbonate

53.00

Triethyl amine

N

H3C

CH3

CH3

101.19

Tartaric acid

OH

OHO

HOO

OH+ +

C4H6O6

150.09

Methanol

NO2

H2N

O O

HN

N

CH3

HOOH

OHO

O OH

Cinitapride Hydrogen Tartrate

C25H36N4O10

552.57

+

Sodium benzene sulphonate

SOO

ONa

C6H5NaO3S

180.16

N

H3C

CH3

CH3 H

Cl+

Triethyl amine Hydrochlorie

C6H16ClN

137.65

+1/2 CO2

22.0

+ 1/2 H2O

9.00




Flow Chart

Stage-1

4-Amino-2-ethoxy-5-nitro-N-(4-piperidyl)benzamide3-Cyclohexane-1-methanolTriethyl amineTartaric acidMethanolCyclo hexane

Cyclo hexane RecMethanol Rec




Material Balance:

Material balance of Cinitapride Hydrogen Tartrate Stage-1



In Kg 4-Amino-2-ethoxy-5nitro-N-(4-piperidyl)benzamide

19.51 Cinitapride Hydrogen Tartrate

35.00

3-Cyclohexene-1-methanol 7.10 Cyclohexane Recovery 84.20 Benzene sulfonyl chloride 11.17 Cyclohexane Loss 4.00 Sodium carbonate 3.35 DMF Recovery 189.00 TEA 24.60 DMF Loss 9.00 Tartaric acid 15.20 Methanol Recovery 222.00 Cyclohexane 88.20 Methanol Loss 11.00 DMF 198.00 Effluent water 819.54 Methanol 233.00 (Water-775,Generated water-

0.56,Sodium benzene sulfonate-10.38,TEA HCl-8.7,Tartaric acid-5.7,Methanol-1,TEA-18.2)

Activated carbon 4.00 Process Emission 1.39 Water 775.00 (Carbon dioxide) Spent carbon 4.00 Total 1379.13 Total 1379.13



6. DAPOXETINE HYDROCHLORIDE


Stage-1

(S)-3-Chloro-1-phenyl propan-1-ol reacts with 1-Napthol in the presence of Di methyl

amine and Isopropanol HCl in the presence of Methanol as a solvent media to give

Dapoxetine Hydrochloride as product.



DAPOXETINE HYDROCHLORIDE

Route of Synthesis:

Stage -1: OH

Cl

3-Chloro-1-phenyl-propan-1-ol

C9H11ClO

170.64

+

OH

Naphthalen-1-ol

C10H8O

144.17

+

Methanol

H3C

HN

CH3

Dimethyl-amine

C2H7N

45.08

Isopropanol.HCl

CH3

CH3HO

HCl

CH3

CH3HO

Isopropanol

C3H8O

60.10

C3H9ClO

95.56

O

NH3C CH3

H

Dapoxetine Hydrochloride

C21H24ClNO

341.87

+ + HCl + H2O

Hydrochloric acid

36.5

18.00




Flow Chart:

Stage-1


(S)-3-Chloro-1-phenyl propan-1-ol 1-NaptholDimethylamineIPA.HCl

Generated waterIsopropanol Rec




Material Balance:

Material Balance of Dapoxetine Hydrochloride Stage-1

Batch Size:80.0Kg Name of the input Quantity


in Kg (S)-3-Chloro-1-phenyl propan-1-ol reacts

40.00 Dapoxetine Hydrochloride 80.00

1-Napthol 34.00 Methanol Recovery 943.00 Dimethylamine 33.00 Methanol Loss 40.00 IsopropanolHCl 55.00 Ethyl acetate Recovery 1334.75 Dimethyl sulfoxide 280.00 Ethyl acetate Loss 70.25 Sodium chloride 34.00 Effluent water 3350.24 Mesyl chloride 50.00 (Water-2925,Generated water-

4.22,Isopropanol-34.2,Mesyl chloride-50, N,N-Dimethyl amino pyridine -0.02,HCl-20.8,DMSO-280,Sodium chloride-34, Methanol-2)

Triethylamine 126.00 Triethylamine Recovery (For Reuse)

126.00

N,N-Dimethyl amino pyridine 0.02 Spent carbon 14.00 Methanol 995.00 Organic Residue 32.78 Ethyl acetate 1405.00 (Organic impurities-22.78,

Methanol-10)

Activated carbon 14.00 Water 2925.00 Total 5991.02 5991.02



7. EPALRESTAT


3-Carboxy methyl rhodanine reacts with 2-methyl cinnamaldehyde in sodium

acetate, acetic acid by using DMF as solvent media to give pure Epalrestat as

Product.



EPALRESTAT

Route of Synthesis:

Stage-1

N

S

S

O

CH2COOH

3-Carboxy methyl rhodanine

C5H5NO3S2

191.23

+

CHO

CH3

2-Methyl-3-phenyl-propenal

C10H10O

146.19

DMF

CH3 N

SS

O

CH2COOH

Epalrestat

C15H13NO3S2

319.40

+ H2O

18.0



EPALRESTAT

Flow Chart:

3-carboxy methyl rhodanine2-Methyl cinnamldehdyeSodium acetateAcetic acidDMF

Stage-1 DMF Rec

EPALRESTAT



EPALRESTAT

Material Balance:

Material balance of Epalrestat Stage-1



In Kg 3-carboxy methyl rhodanine 72.00 Epalrestat 120.00 2-Methyl cinnamldehdye 55.00 DMF Recovery 2801.00 Sodium acetate 78.00 DMF Loss 149.00 Acetic acid 797.00 Acetic acid Recovery 758.00 DMF 2981.00 Acetic acid Loss 39.00 Activated carbon 19.00 Effluent water 4376.77 Water 4291.00 (Water-4291,Generated water-

6.77,DMF-1,Sodium acetate-78)

Spent carbon 19.00 Organic Residue 30.23 (Organic impurities-0.23,DMF-30) Total 8293.00 Total 8293.00



8. ESZOPICLONE


Stage-1

O-Phenylenediamine reacts with glyoxal, potassium permanganate, Hydrochloric

acid in presence of Toluene as a solvent media to give Stage-1 as a product.

Stage-2

Stage-1 product is condensed with 2-Amino-5-chloropyridine in Acetonitrile and

cyclized in Toluene then reduced with Sodium borohydride to give Stage-2 as a

product.

Stage-3

Stage-2 product reacts with N-Methyl piperazine and Triphosgene and Potassium

chloride in presence of Isopropyl alcohol as a solvent media to give Eszopiclone as a

product.



ESZOPICLONE

Route of Synthesis

Stage-1

NH2

NH2

Benzene-1,2-diamine

C6H8N2

108.14

+

Glyoxal

OO

58.04

C2H2O2

+ 2 KMnO4

Potassium permanganate

316.07

+ 2 HCl

Hydrochloric acid

73.00

+ H2O

18.00

Toluene

N

N

O

O

O

Furo[3,4-b]pyrazine-5,7-dioneC6H2N2O3

150.09

+ 2 KCl

Potassium chloride

149.10

+2 CO2

88.00

Carbon dioxide

+ 2 MnO2

Manganese dioxide173.87

+ 6 H2

12.00



Stage-2

N

N

O

O

O

Furo[3,4-b]pyrazine-5,7-dioneC6H2N2O3

150.09

N

Cl

NH2

5-Chloro-pyridin-2-ylamine

++ NaBH4

Sodium borohydride

37.83

+ 3 H2O

3X18=54.0

Acetonitrile

N

N

N

N

Cl

OH

O

+ H2O

18.00

+ NaBO3

Sodium perborate

81.80

+ 4 H2

8.00

C5H5ClN2

128.56

6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7-dihydro-pyrrolo[3,4-b]

pyrazin-5-oneC11H7ClN4O2

262.65



Stage-3

N

N

N

N

Cl

OH

O

6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7-dihydro-pyrrolo[3,4-b]

pyrazin-5-oneC11H7ClN4O2

262.65

+

N-Methyl piperazine

N

HN

CH3

C5H12N2

100.16

Triphosgene

Cl

ClCl

O

O

OCl

ClCl

C3Cl6O3

1/3X296.75=98.91

+ + K2CO3

138.21

Potassium carbonate

N

N

N

N

Cl

O

O

N

O

N

CH3

Eszopiclone

C17H17ClN6O3

388.81

Isopropyl alcohol

+ CO2

44.00

Carbon dioxide

+ H2O

18.00

+ 2 KCl

Potassium chloride

2X74.5=149.0



ESZOPICLONE

Flow Chart

Stage-1

Stage-2

Stage-3

ESZOPICLONE

O-Phenylenediamine Glyoxal Potassium permanganateToluene

Toluene Rec

Stage-12-Amino-5-chloropyridine AcetonitrileSodium borohydride Toluene

Toluene RecEffluent water

Stage-2N-Methyl piperazineTriphosgenePotassium carbonateIPA

IPA RecEffluent water



ESZOPICLONE

Material Balance:

Material balance of Eszopiclone Stage-1



In Kg O-Phenylene diamine 24.20 Stage-1 19.70 Glyoxal 7.60 Toluene Recovery 210.80 Potassium permanganate 158.00 Toluene Loss 9.20 Toluene 230.00 EDC Recovery 41.80 Hydrochloric acid 33.00 EDC Loss 2.20 Sodium bisulfate 35.00 Acetic anhydride Recovery 159.60 Ethylene chloride 44.00 Acetic anhydride Loss 8.40 Acetic anhydride 168.00 Effluent water 358.49

Sodium chloride

10.00

(Water-127.64,Potassium chloride-74.53,Manganese dioxide-86.90,HCl-23.42,Sodium bisulfate-35,Sodium chloride-10, Toluene-1)

Hyflow 2.50 Spent hyflow 2.50 Water 130.00 Process Emissions 17.52

(Carbon dioxide-11.52,Hydrogen-

6)

Organic Residue 12.09

(Organic impurities-2.09,Toluene-

10)







In Kg Stage-1 19.70 Stage-2 10.90 2-Amino-5-Chloropyridine 16.90 Toluene Recovery 148.00 Sodium boro hydride 6.00 Toluene Loss 6.00 Hydrochloric acid 27.00 Acetonitrile Recovery 213.75 Acetic acid 1.60 Acetonitrile Loss 11.25 Acetonitrile 225.00 Chloroform Recovery 1453.50 Toluene 160.00 Chloroform Loss 76.50 Chloroform 1530.00 1,4-Dioxane Recovery 28.80 1,4-Dioxane 30.00 1,4-Dioxane Loss 1.30 Activated carbon 6.00 Effluent water 1117.86 Water 1080.00 (Water-1072.92,Generated water-

2.37,Sodium per borate-12.97, HCl-27,Acetic acid-1.60,Toluene-1)

Spent carbon 6.00 Process Emissions 1.26 (Hydrogen-1.26) Organic Residue 26.08

Organic Impurities-21.08,

Toluene-5)

Total 3102.20 Total 3102.20






In Kg Stage-2 10.90 Eszopiclone

10.00

N-Methyl piperazine 26.00 MDC Recovery 3304.50 Triphosgene 26.00 MDC Loss 175.50

Potassium carbonate 83.00 Methyl tertiary butyl ketone

Recovery 183.35

Tetrabutyl ammonium bromide 1.00 Methyl tertiary butyl ketone Loss 9.65 1,4-Toluyl tartaric acid monohydrate

45.00 Methanol Recovery

410.88

Sodium hydroxide 45.00 Methanol Loss 17.12 Methylene chloride 3510.00 Acetone Recovery 779.00 Methyl tertiary butyl ketone 193.00 Acetone Loss 41.00 Methanol 428.00 Isopropyl alcohol Recovery 153.60 Acetone 820.00 Isopropyl alcohol Loss 6.40

Isopropyl alcohol 160.00 Effluent water 1085.83

Activated carbon 1.50 (Water-900,Generated water-2.36,Potassium chloride-89.47, Tetra butyl ammonium bromide-1,1,4-Toluyl tartaric acid mono hydrate-45, sodium hydroxide-45, Methanol-1,Acetone-2)

Water 900.00 Spent carbon 1.50 Process Emissions 26.42 (carbon dioxide-26.42) Organic Residue 44.65

(Organic impurities-14.65,MDC-

30)

Total 6249.40 Total 6249.40



9. FLUCONAZOLE


Stage-1

1-[2-(2, 4-Difluorophenyl-2, 3-epoxypropyl]-1H-[1, 2, 4] triazole is reacted with 1,2,4-

triazole in the presence of Potassium carbonate, Acetone and Ethyl acetate to give

Fluconazole as product.



FLUCONAZOLE

Route of Synthesis:

Stage-1

F

F

O N

NN

1-[2-(2,4-Difluoro-phenyl)-oxiranylmethyl]-1H-[1,2,4]triazole

C11H9F2N3O

237.21

+

1,2,4-Triazole

NH

NN

C2H3N3

2X69.07=138.14

Ethyl acetate

Acetone

2

F

F

N

NN

N

NN OH

Fluconazole

C13H12F2N6O

306.27



FLUCONAZOLE

Flow Chart:

1[2-(2,4-Difluorophenyl)-2,3-epoxy propyl)-1H-1,2,4-Triazole1,2,4-TriazolePotassium carbonateAcetone

Stage-1 Acetone Rec

FLUCONAZOLE



FLUCONAZOLE

Material Balance:

Material balance of Fluconazole Stage-1



In Kg 1[2-(2,4-Difluorophenyl)-2,3-epoxy propyl)-1H-1,2,4-Triazole

77.45 Fluconazole

100.00

1,2,4-Triazole 45.10 Acetone Recovery 600.00 Sodium sulphate 130.00 Acetone Loss 30.00 Acetone 630.00 Ethyl acetate Recovery 1013.00 Ethyl acetate 1076.00 Ethyl acetate Loss 53.00 Activated carbon 10.00 Spent carbon 10.00 Inorganic solid waste 130.00 (Sodium sulphate) Organic Residue 32.55 (Organic impurities-22.55,

Ethylacetate-10)

Total 1968.55 Total 1968.55



10. IRON SUCROSE


Stage-1

Ferric chloride reacts with Sucrose in presence of Sodium carbonate, Sodium

hydroxide to give Iron Sucrose as a product.



IRON SUCROSE

Route of Synthesis:

Stage-1

5 FeCl3

Ferric chloride

5X162.3=811.5

+ 2 Na2CO3

Sodium carbonate

2X106=212.0

+ 10 H2O

10X18=180.0

+

C12H22O11

Sucrose

OH

OH

HO

O

HO

O

OHOH

HO

HOO

+ NaOH

SodiumHydroxide

40.0

Iron sucrose

Na2Fe5O8(OH) 3H2OC12H22O11

342.00

866.00

+ 3 NaCl

175.33

+ 12 HCl

437.53

+ H2O

18.0

+ 2 CO2

2X44=88.0



IRON SUCROSE

Flow Chart

Stage-1

IRON SUCROSE

Ferric chloride SucroseSodium carbonateSodium hydroxide

Effluent water



IRON SUCROSE

Material Balance:

Material balance of Iron Sucrose Stage-1



In Kg Ferric Chloride 93.71 Iron Sucrose 100.00 Sodium carbonate 24.45 Effluent water 2008.54 Sucrose 45.00 (Water-1930.22,Sodium chloride-

20.22,HCl-50.52,Generated water-2.07,Sucrose-5.51)

Water 1951.00 Process Emissions 5.62 (Carbon dioxide-5.62) Total 2114.16 Total 2114.16



11. ITOPRIDE HYDROCHLORIDE


Stage-1

3, 4-Dimethoxybenzoic acid reacts with Thionyl chloride, 4-(N, N-Di methyl amino

ethoxy) benzyl amine in presence of Toluene, Methanol as a solvent media to give

Itopride Hydrochloride as a product.



ITOPRIDE HYDROCHLORIDE

Route of Synthesis

Stage-1

OCH3

H3CO

OH

O

3,4-Dimethoxy-benzoic acid

C9H10O4

182.17

+ SOCl2

Thionyl chloride

118.97

NH2

ON

CH3

H3C

[2-(4-Aminomethyl-phenoxy)-ethyl]-dimethyl-amine

C11H18N2O

194.27

+

Toluene

HN

ON

CH3

H3C O

OCH3

OCH3

N-[4-(2-Dimethylamino-ethoxy)-benzyl]-3,4-dimethoxy-benzamide

Hydrochloride

+ SO2

Sulphurdioxide

64.06

+ HCl

Hydrochloric acid36.5

HCl

C20H27ClN2O4

394.89




Flow Chart

Stage-1


3,4-Dimethoxybenzoic acidThionyl chloride4-(N,N-Dimethylaminoethoxy)BenzylamineMethanolIsopropyl alcohol

Methanol RecIsopropyl alcohol




Material Balance:

Material balance of Itopride Hydrochloride Stage-1



In Kg 3,4-Dimethoxybenzoic acid 47.90 Itopride Hydrochloride 93.00 Thionyl chloride 28.01 Toluene Recovery 1394.00 4-(N,N-di methyl amino ethoxy)benzyl amine

45.74 Toluene Loss 73.00

Hydrochloric acid 10.50 Chloroform Recovery 427.00 IPA.HCl 94.00 Chloroform Loss 22.00 Toluene 1478.00 IPA Recovery 978.80 Chloroform 449.00 IPA Loss 47.00 IPA 943.00 Methanol Recovery 481.00 Methanol 506.00 Methanol Loss 25.00 Activated carbon 16.00 Effluent water 631.29 Water 600.00 (Water-600,Hydrochloric acid-

30.29,Toluene-1)

Spent carbon 16.00 Process Emission 15.06 (Sulfur dioxide) Organic Residue 15.00 (Organic impurities-5,Toluene-10) Total 4218.15 Total 4218.15



12. KETOROLAC TROMETHAMINE


Stage-1

Ketrolac reacts with Tromethamine in presence of Acetone, Methanol to give

ketorolac tromethamine as product.



KETOROLAC TROMETHAMINE

Route of Synthesis:

Stage-1

N

O

OH

OKetrolac

C15H13NO3

255.27

+

HONH2

HO

HO

Tromethamine

C4H11NO3

121.14

Acetone

N

O

OH

O

HONH2

HO

HO

KETOROLAC TROMETHAMINEC19H24N2O6

376.41




Flow Chart:

KetorolacTromethamineActivated carbonMethanolAcetone

Stage-1 Acetone Rec





Material Balance:

Material balance of Ketorolac tromethamine Stage-1



In Kg Ketorolac 79.86 Ketorolac tromethamine 103.00 Tromethamine 33.14 Methanol Recovery 251.00 Activated carbon 5.00 Methanol Loss 13.00 Methanol 265.00 Acetone Recovery 2145.00 Acetone 2278.00 Acetone Loss 112.00 Water 63.00 Effluent water 65.00 (Water-63,Methanol-1,Acetone-1) Spent carbon 5.00 Organic Residue 30.00 (Organic impurities-10,Acetone-

20)

Total 2724.00 Total 2724.00



13. LEVOCETIRIZINE DIHYDROCHLORIDE


1-[(4-Chlorophenyl) phenyl methyl]-4-[(phenyl sulphonyl] piperazine is deprotected

with 4-Hydroxy benzoic acid in Hydro bromic acid then is condensed with 2(2-

Chloroethoxy acetamide) in presence of Sodium carbonate in toluene and is reacted

with sodium hydroxide and Hydrochloric Acid in acetone to give Levocetrizine Di

hydrochloride as product.



LEVOCETIRIZINE DIHYDROCHLORIDE

Route of Synthesis:

Stage-1

N N S

O

O

Cl

1-Benzenesulfonyl-4-[(4-chloro-phenyl)-phenyl-methyl]-piperazine

C23H23ClN2O2S

426.96

+OH

OHO

4-Hydroxy benzoic acid

C7H6O3

138.12

+ ClO

NH2

O

2-(2-Chloro-ethoxy)-acetamide

C4H8ClNO2

137.56

+ Na2CO3

Sodium carbonate

106.0

+ HBr

Hydrobromic acid

80.91

+ 2NaOH

Sodium hydroxide

2X40=80.0

Acetone

N N

Cl

OOH

O

HCl

2

Levocetrizine Dihydrochloride

C21H27Cl3N2O3

461.89

+ OH

ONaO

Sodium salt of 4-Hydroxy benzoic acid

C7H5NaO3

160.10

+

SO O

Br

Benzene sulfonyl bromide

C6H5BrO2S

221.07

+ 2NaCl

2X58.5=117.0

+ NaHCO3

84.01

+ NH4Cl

53.49

+ H2O

18.0

+ 4HCl

Hydrochloric acid

4X36.5=146.0




Flow Chart:

1-[((4-Chlorophenyl)phenyl)methyl]-4-[(phenylsulphonyl)]piperazine2(2-Chloroethoxy )acetamide4-Hydroxy benzoic acidHydrobromic acidToluene

Stage-1 Toluene Rec

LEVOCETRIZINE DIHYDROCHLORIDE




Material Balance:

Material balance of Levocetirizine Dihydrochloride Stage-1



In Kg 1-[((4-Chlorophenyl)phenyl)methyl]-4-[(phenylsulphonyl)]piperazine

46.20 Levocetirizine Dihydrochloride 50.00

2(2-Chloroethoxy )acetamide 14.90 Toluene Recovery 1440.00 4-Hydroxy benzoic acid 16.00 Toluene Loss 75.00 Hydrobromic acid 8.80 MDC Recovery 1757.00 Sodium hydroxide 8.70 MDC Loss 93.00 Hydrochloric acid 15.80 Acetone Recovery 442.00 Sodium carbonate 11.50 Acetone Loss 23.00 Potassium iodide 1.70 Effluent water 2302.24 Toluene 1515.00 (Water-2270,Generated water-

1.94,Sodium chloride-12.7, Sodium bicarbonate-9.11, Ammonium chloride-5.79, Potassium Iodide-1.7,Toluene-1)

MDC 1860.00 Spent carbon 4.00 Acetone 465.00 Organic Residue 51.36 Activated carbon 4.00 (Sodium salt of 4-Hydroxy

benzoic acid-18.54,Benzene sulfonyl bromide-22.82,MDC-10)

Water 2270.00 Total 6237.60 Total 6237.60



14. LEVOSULPRIDE


Stage-1

Methyl-2-methoxy-5-sulfamoyl benzoate is reacted with 1-ethyl-2-amino methyl

pyrrolidine in ethylene glycol, Methanol and Activated carbon to give Levosulpride as

product.



LEVOSULPRIDE

Route of Synthesis:

Stage-1

OCH3

COOCH3S

OO

H2N

2-Methoxy-5-sulfamoyl-benzoic acid methyl ester

C9H11NO5S

245.25

+

1-Ethyl-2-aminomethylpyrrolidine

NH2N

C7H16N2

128.22

Methanol

OCH3

S

OO

H2N NH

N

CH3O

Levosulpride

C15H23N3O4S

341.43

+ CH3OH

32.0



LEVOSULPRIDE

Flow Chart:

Methyl-2-methoxy-5-sulfamoyl benzoate1-Ethyl-2-amino methyl pyrrolidineMethanol

Stage-1 Methanol Rec

LEVOSULPRIDE



LEVOSULPRIDE

Material Balance:

Material balance of Levosulpride Stage-1



In Kg Methyl-2-methoxy-5-sulfamoyl benzoate

97.68 Levosulpride 136.00

1-Ethyl-2-amino methyl pyrrolidine

51.06 Ethylene glycol Recovery 276.00

Ethylene glycol 290.00 Ethylene glycol Loss 14.00 Methanol 1900.00 Methanol Recovery 1817.74 Activated carbon 5.00 Methanol Loss 95.00 Spent carbon 5.00 Total 2343.74 Total 2343.74



15. LINEZOLID


Stage-1:

N-[3-pthalimido-2R-Hydroxy propyl]-3-(fluoro-4-morpholinyl) aniline is treated with

carbonyl diimidazole, Hydrazine hydrate and acetic anhydride in the presence of

MDC and Methanol to give Linezolid as product.



LINEZOLID

Route of Synthesis:

Stage-1

O N

F

NH

N

OH

O

O

2-[3-(3-Fluoro-4-morpholin-4-yl-phenylamino)-2-hydroxy-propyl]-isoindole-1,3-dione

C21H22FN3O4

399.42

+

Carbonyl diimidazole

O

N

HNNH

N

C7H6N4O

162.15

+

Hydrazine hydrate

H2NNH2H

OH

H6N2O

50.06

+

Acetic anhydride

OO

O

C4H6O3

102.09

MDC

O N

F

NO

O

HN CH3

O

Linezolid

C16H20FN3O4

337.35

+

Imidazole

N

HN

2

C3H4N2

2X68.08=136.16

+ CH3COOH

60.0

+

Phthalazine -1,4-diol

N

N

OH

OH

C8H6N2O2

162.15

+ H2O

18.0



LINEZOLID

Flow Chart:

N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl anilineCarbonyl diimidazoleHydrazine HydrateMethanol


LINEZOLID



LINEZOLID

Material Balance:

Material balance of Linezolid Stage-1



In Kg N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl aniline

116.55 Linezolid 90.00

Carbonyl di imidazole 41.25 Methanol Recovery 705.00 Hydrazine Hydrate 13.35 Methanol Loss 37.00 Acetic anhydride 27.23 MDC Recovery 2546.00 Methanol 778.00 MDC Loss 134.00 MDC 2707.00 Ethyl acetate Recovery 765.00 Activated carbon 3.00 Ethyl acetate Loss 40.00 Ethyl acetate 805.00 Methanol + MDC 49.00 Acetone 1548.00 Acetone Recovery 1471.00 Water 3400.00 Acetone Loss 77.00 Effluent water 3456.13 (Water-3400,Generated water-

4.8,Acetic acid-16,Methanol-1,Imidazole-34.33)

Spent carbon 3.00 Organic Residue 66.25 (Phthalazine-1,4-diol-

43.25,Organic impurities-11, MDC-2,Methanol-10)

Total 9439.38 Total 9439.38



16. MOSAPRIDE CITRATE DIHYDRATE


2-Amino methyl-4-(4-fluorobenzyl0morpholine is condensed with 4-amino-5-chloro-2-

ethoxy benzoic acid in presence of Triethyl amine in Ethyl chloro formate and MDC

then is purified with Methanol and is reacted with citric acid to give Mosapride Citrate

Dihydrate as product.



MOSAPRIDE CITRATE DIHYDRATE

Route of Synthesis:

Stage-1

F

N

O

NH2

C-[4-(4-Fluoro-benzyl)-morpholin-2-yl]-methylamine

C12H17FN2O

224.27

+ O

OHCl

H2N

O

4-Amino-5-chloro-2-ethoxy-benzoic acidC9H10ClNO3

215.63

COOH

HO COOH

COOH+

Citric acid

C6H8O7

192.12

+ H2O

Water18.0

MDC

AcetoneO

NHCl

H2N

O

N

O

F

COOH

HO COOH

CHOOH2H2O

Mosapride Citrate Dihydrate

C27H37ClFN312

650.01




Flow Chart:

2-Amino methyl-4-(4-fluorobenzyl)morpholine4-Amino-5-chloro-2-ethoxy benzoic acidCitric acidMDC

Stage-1 MDC Rec

MOSAPRIDE CITRATE DIHYDRTAE




Material Balance:

Material balance of Mosapride citrate dihydrate Stage-1



In Kg 2-Amino methyl-4-(4-fluorobenzyl)morpholine

35.87 Mosapride citrate dihydrate 75.00

4-Amino-5-chloro-2-ethoxy benzoic acid

24.87 MDC Recovery 1762.00

Citric acid 22.16 MDC Loss 93.00 Ethyl chloro formate 19.00 Acetone Recovery 224.00 TEA 33.00 Acetone Loss 11.00 MDC 1865.00 Methanol Recovery 199.00 Acetone 235.00 Methanol Loss 10.00 Methanol 210.00 Effluent water 2285.90 Activated Carbon 16.00 (Water-2232.9,TEA-33,Ethyl

chloroformate-19,Methanol-1)

Water 2235.00 Spent carbon 16.00 Organic Residue 20.00 (Organic impurities-10,MDC-10) Total 4695.90 Total 4695.90



17. ONDANSETRON HYDROCHLORIDE DIHYDRATE


3-Dimethylaminomethyl-9-methyl-1, 2, 3, 9-tertahydro-carbazol-4-one reacts with 2-

methyl imidazole, Hydrochloric acid in the presence of Methanol as solvent media to

give Ondansetron Hydrochloride Di hydrate as product.



ONDANSETRON HYDROCHLORIDE DIHYDRATE

Route of Synthesis:

Stage-1

N

O

CH3

NCH3

CH3

3-Dimethylaminomethyl-9-methyl-1,2,3,9-tetrahydro-carbazol-4-one

C16H20N2O

256.34

+

2-Methyl imidazole

N

NH

C4H6N2

82.10

+ HCl

Hydrochloric acid

36.5

+ 2H2O

Water

2X18=36.0

Methanol

N

O

CH3

NN

H3C

HCl

2H2O

Ondansetron Hydrochloride Dihydrate

C18H24ClN3O3

365.86

+

Dimethyl amine

HN

C2H7N

45.08




Flow Chart:

3-Dimethylamino methyl-9-methyl-1,2,3,9-tetrahydro carbazole-4-one2-Methyl imidazoleHydrochloric acidMethanol






Material Balance:

Material balance of Ondansetron Hydrochloride Dihydrate Stage-1



In Kg 3-Dimethylamino methyl-9-methyl-1,2,3,9-tetrahydro carbazole-4-one

10.50 Ondansetron Hydrochloride Dihydrate

15.00

2-Methyl imidazole 4.00 Methanol Recovery 68.00 Hydrochloric acid 6.40 Methanol Loss 3.00 Methanol 72.00 Effluent water 628.27 Activated carbon 2.50 (Water-620.53,Dimethyl amine-

1.84,Hydrochloric acid-4.9, Methanol-1)

Water 622.00 Spent carbon 2.50 Organic Residue 0.63 Total 717.40 Total 717.40



18. PREGABALIN


Stage-1

3-(Amino methyl)-5-methyl hexanoic acid reacts with Mandelic acid and with Liq.

Ammonia to give Pregabalin as product.



PREGABALIN

Route of Synthesis:

Stage-1

NH2

COOH

3-Aminomethyl-5-methyl-hexanoic acid

C8H17NO2

159.23

Mandelic acid

Liq.Ammonia

NH2

COOH

Pregabalin

C8H17NO2

159.23

PREGABALIN

Flow Chart:

3-(Amino methyl)-5-methyl hexanoic acidMandelic acidCitric acid monohydrateMethanol


PREGABALIN



PREGABALIN

Material Balance:

Material balance of Pregabalin Stage-1



In Kg 3-(Amino methyl)-5-methyl hexanoic acid

99.10 Pregabalin

95.00

Mandelic acid 129.10 Methanol Recovery 1380.00 Liq. Ammonia 14.60 Methanol Loss 73.00 Citric acid monohydrate 74.60 Mandelic acid Recovery & Reuse 129.10 Methanol 1464.00 Effluent water 1511.80 Activated carbon 8.00 (Water-1421.6,Citric acid

monohydrate-74.6,Liq-Ammonia-14.6,Methanol-1)

Water 1421.60 Spent carbon 8.00 Organic Residue 14.10 (organic Impurities-4.1,Methanol-

10)

Total 3211.00 Total 3211.00



19. RACECADOTRIL


Stage-1

2-Benzylacryloyl chloride is reacted with Glycine benzyl ester-p-

tosylate,Triethylamine and Thioacetic acid to give Racecadotril (Pharma) as product.



RACECADOTRIL

Route of Synthesis:

Stage-1:

CH2

Cl

O

2-Benzyl-acryloyl chloride

C10H9ClO

180.63

O

ONH2

CH3

SO OOH

Glycine benzyl ester p-tosylate

C16H19NO5S

337.39

+ +

Triethyl amine

N

H3C

CH3

CH3

C6H15N

101.19

+

Toluene

+N

H3C

CH3

CH3

Triethyl amine Hydrochloride

H

Cl

+

H3C

SO3H

C7H8O3S

172.20C6H16ClN

137.65

P-Toluene sulfonic acid

H3C SH

O

Thioacetic acid

C2H4OS

76.12

H2CNH

OO

OS

CH3

O

Racecadotril(Pharma)

C21H23NO4S

385.48



RACECADOTRIL

Flow Chart:

Stage-1

2-Benzylacryloyl chlorideGlycine benzyl ester-p-tosylateThioacetic acidTriethylamineToluene

Toluene RecTriethylamine HCl

RACECADOTRIL



RACECADOTRIL

Material Balance:

Material Balance of Racecadotril Stage-1



in Kg 2-Benzylacryloyl chloride 58.00 Racecadotril 80.00 Glycine benzyl ester-p-tosylate 70.00 Isopropyl alcohol Recovery 1063.00 Thioacetic acid 30.00 Isopropyl alcohol Loss 57.00 Triethylamine 100.00 Toluene Recovery 365.00 Sodium bicarbonate 16.00 Toluene Loss 15.00 Sodium chloride 6.50 n-Hexane Recovery 460.00 Isopropyl alcohol 1130.00 n-Hexane Loss 19.00 n-Hexane 480.00 Methanol Recovery 978.00 Toluene 380.00 Methanol Loss 50.00 Methanol 1030.00 Effluent water 1361.22 Activated carbon 10.00 (Water-1300,p-Toluene sulfonic

acid-35.72,Sodium bicarbonate-16, Sodium chloride-6.5,Toluene-1, Methanol-2)

Triethylamine HCl [Recovered for reuse]

136.10

Water 1300.00 Spent carbon 10.00 Organic Residue 14.18 (Organic impurities-3.18,IPA-10,n-

Hexane-1)

Total 4610.50 Total 4610.50



20. TAMSULOSIN HYDROCHLORIDE


(R)-5-[[2-(2-Ethoxy phenoxy) ethyl) amino] propyl]-2-methoxy benzene reacts with

hydrochloric acid in the presence of methanol as solvent media to give Tamsulosin

Hydrochloirde as product.



TAMSULOSIN HYDROCHLORIDE

Route of Synthesis:

Stage-1:

S

H3CO

O O

H2N

HN

CH3

O

OH3C

C20H28N2O5S• HCl.

Tamsulosin hydrochloride

HCl

444.98

S

H3CO

O O

H2N

HN

CH3

O

OH3C

5-{2-[2-(2-Ethoxy-phenoxy)-ethylamino]-propyl}-2-methoxy-benzenesulfonamide

+ HCl

Hydrochloric acid

36.5

C20H28N2O5S

408.51

Methanol




Flow Chart:

Stage-1

TAMSULOSIN HCl

(R)-5-[[2-(2-Ethoxy phenoxy)ethyl)amino]propyl]-2-methoxy benzeneHydrochloric acidMethanolAcetone

Methanol RecAcetone Rec




Material Balance:

Material Balance of Tamsulosin Hydrochloride Stage-1



in Kg (R)-5-[[2-(2-Ethoxy phenoxy) ethyl)amino]propyl]-2-methoxy benzene 19.30

Tamsulosin Hydrochloride 20.00

Hydrochloric acid 13.30 Methanol Recovery 180.00 Methanol 190.00 Methanol Loss 8.00 Acetone 310.00 Acetone Recovery 294.50 Water 22.00 Acetone Loss 15.50 Effluent water 34.37

(Water-22,Hydrochloric acid-10.37, Methanol-1,Acetone-1)


(Organic impurities-0.23,Methanol-

2)




21. TIZANIDINE HYDROCHLORIDE


Stage-1

4-Amino-5-chloro-2, 1, 3-benzothiadiazole is condensed with 1-acetyl imidazolin-2-

one reacts with phosphorous oxychloride and sodium hydroxide in water to give

stage-1 as product.

Stage-2

Stage-1 product reacts with Hydrochloric acid in methanol to give Stage-2 as

product.

Stage-3

Stage-2 product is purified by methanol,caron to give Pure Tizianidine Hydrochloride

as product.



TIZANIDINE HYDROCHLORIDE

Route of Synthesis:

Stage-1

N

S

N

Cl

NH2

5-Chloro-benzo[1,2,5]thiadiazol-4-ylamine

C6H4ClN3S

185.63

+

1-Acetyl-imidazolidin-2-one

NHN

O

O

C5H8N2O2

128.13

+ POCl3

Phosphorous oxychloride

153.33

+ 4NaOH

Sodium hydroxide

4X40=160.0

Water

N

S

N

Cl

NHN

NH

Tizianidine

C9H8ClN5S

253.71

+ CH3COOH

60.0

+ 3NaCl

3X58.5=175.5

+ NaH2PO4

119.98

+ H2O

18.0



Stage-2

N

S

N

Cl

NHN

NH

Tizianidine

C9H8ClN5S

253.71

+ HCl

Hydrochloric acid

36.50

Methanol

N

S

N

Cl

NHN

NH

HCl

Tizianidine Hydrochloride (Crude)

C9H9Cl2N5S

290.21

Stage-3

N

S

N

Cl

NHN

NH

HCl

Tizianidine Hydrochloride (Crude)

C9H9Cl2N5S

290.21

Methanol

N

S

N

Cl

NHN

NH

HCl

Tizianidine Hydrochloride (Pure)

C9H9Cl2N5S

290.21

Water




Flow Chart:

4-Amino-5-chloro-2,1,3-benzo-thiadiazole1-Acetyl-imidazolidin-2-onePhosphorous oxy chlorideMethanol



Stage-1Hydrochloric acidMethanol


Stage-2MethanolActivated carbon

TIZIANIDINE HYDROCHLORIDE




Material Balance:

Material balance of Tizianidine Hydrochloride Stage-1

Batch Size: 153.0 Kg Name of the input Quantity


In Kg 5-chloro-2,1,3-benzo-thiadiazole-4-ylamine

115.00 Stage-1 155.00

1-Acetyl-imidazolidin-2-one 78.20 Methanol Recovery 4360.00 Phosphorous oxy chloride 94.00 Methanol Loss 229.00 Sodium hydroxide 98.00 Effluent water 5311.00 Methanol 4590.00 (Water-5080,Generated water-

11,Acetic acid-37,Sodium chloride-108,Sodium di hydrogen phosphate-74,Methanol-1)

Activated carbon 10.00 Spent carbon 10.00 Water 5080.00 Organic Residue 0.20 Total 10065.20 Total 10065.20


Batch Size: 153.0 Kg Name of the input Quantity


In Kg Stage-1 155.00 Stage-2 177.00 Hydrochloric acid 23.00 Methanol Recovery 332.00 Sodium sulphate 98.00 Methanol Loss 17.00 Acetic acid 31.00 Effluent water 9149.00 Methanol 350.00 (Water-9050,Methanol-1,Sodium

sulphate-98)

Activated carbon 15.00 Spent carbon 15.00 Water 9050.00 Organic Residue 32.00 Total 9722.00 Total 9722.0






In Kg Stage-2 177.00 Tizianidine Hydrochloride 153.00 Methanol 590.00 Methanol Recovery 539.00 Sodium hydroxide 90.00 Methanol Loss 29.00 Activated carbon 15.00 Effluent water 411.00 Water 320.00 (Water-320,Methanol-1,sodium

hydroxide-90) 0

Spent carbon 15.00 Organic Residue 45.00 (Organic impurities-35,

Methanol-10)

Total 1192.00 Total 1192.00



22. TOPIRAMATE

Process Description

Stage-1

(D)-Fructose reacts with Acetone in presence of in presence of Sulfuric acid

Isopropyl alcohol and n-Hexane as a solvent media to give Stage-1 as a product.

Stage-2

Stage-1 product reacts with Sulfuryl chloride and further reacts with Ammonia in

presence of Ethyl acetate as a solvent media to give Topiramate as a product.



TOPIRAMATE

Route of Synthesis

Stage-1

(D)-Fructose

OH

HO

OHHO

OH O

C6H12O6

180.16

+

Acetone

H3C

O

CH3

2X58.08=116.16

C3H6O

2H2SO4

2,2,7,7-Tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4',5'-d]

pyran-3a-yl)-methanol

O

O

O

H3C

H3CO

OCH3

CH3

OH

C12H20O6

260.28

+ 2 H2O

2X18=36.00



Stage-2

2,2,7,7-Tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4',5'-d]

pyran-3a-yl)-methanol

O

O

O

H3C

H3CO

OCH3

CH3

OH

C12H20O6

260.28

+

Sulfuryl chloride

S

O

O

Cl Cl

134.97

+ NH3

Ammonia

17.03

+ NaOH

Sodium hydroxide

40.00

Ethyl acetate

O

O

O

H3C

H3CO

OCH3

CH3

OS

NH2

OO

Topiramate

C12H21NO8S

339.36

+ NaCl

Sodium chloride

58.44

+ HCl

Hydrochloric acid

+ H2O

18.00

36.5



TOPIRAMATE

Flow Chart

Stage-1

Stage-2

TOPIRAMATE

(D)-FructoseAcetoneSulfuric acidIPAn-Hexane

IPA Recn-Hexane RecEffluent water

Stage-1Sulfuryl chlorideAmmoniaEthyl acetate

Ethyl acetate Rec



TOPIRAMATE

Material Balance:

Material Balance of Topiramate Stage-1

Batch Size: 25.0Kgs Name of the input Quantity


in Kg D-Fructose 50.00 Stage-1 50.00 Acetone 317.00 Isopropyl alcohol Recovery 11.00 Sodium hydroxide 38.00 Isopropyl alcohol Loss 1.00 Isopropyl alcohol 12.00 n-Hexane Recovery 79.00 n-Hexane 83.00 n-Hexane Loss 4.00 Water 38.00 Acetone Recovery 257.00 Acetone Loss 16.00 Effluent water 86.00

(Water-38,Generated water-10,

Sodium hydroxide-38)


(Organic Impurities-24 Acetone-

10)




Material Balance of Topiramate Stage-2



in Kg Stage-1 50.00 Topiramate 25.00 Sulfuryl chloride 53.00 Ethyl acetate Recovery 256.00 Ammonia 3.26 Ethyl acetate Loss 14.00 Sodium hydroxide 7.70 Toluene Recovery 1652.00 Sodium chloride 12.30 Toluene Loss 87.00 Pyridine 34.00 MDC Recovery 630.00 Sodium carbonate 5.00 MDC Loss 33.00 Hydrochloric acid 10.00 IPA Recovery 108.00 MDC 665.00 IPA Loss 6.00 Toluene 1740.00 Pyridine Recovery 34.00 Ethyl acetate 270.00 Effluent water 2024.75 IPA 115.00 (Water-1950,Generated water-

0.21,Sodium carbonate-5, Hydrochloric acid-17,Sulfuryl chloride-27, Sodium chloride-23.54,Toluene-1,IPA-1)

Activated carbon 4.00 Spent carbon 4.00 Water 1950.00 Organic Residue 45.51

(Organic impurities-43.51,

MDC-2)

Total 4919.26 Total 4919.26



23. ZOTEPINE


Stage-1

8-Chloro-11H-dibenzo [b,f]thipine-10-one is condensed with (2-Chloroethyl)-dimethyl

amine hydrochloride in the presence of Potassium carbonate in MTBE to give

Zotepine as product.



ZOTEPINE

Route of Synthesis:

Stage-1

S

O

Cl

8-Chloro-11H-dibenzo[b,f]thiepin-10-one

C14H9ClOS

260.74

+ ClN

CH3

CH3

HCl

(2-Chloro-ethyl)-dimethyl-amine; hydrochloride

C4H11Cl2N

144.04

+ K2CO3

Potassium carbonate

138.21

MIBK

S

O

Cl

N

CH3

CH3

Zotepine

C18H18ClNOS

331.86

+ 2KCl

2X74.55=149.10

+ CO2

44.0

+ H2O

18.0



ZOTEPINE

Flow Chart:

8-Chloro-11H-dienzo[b,f]thiepine-10-one2-(Chloro ethyl) dimethyl amine hydrochloridePotassium carbonateMIBK

Stage-1 MIBK Rec

ZOTEPINE



ZOTEPINE

Material Balance:

Material balance of Zotepine Stage-1

Batch Size:10.0Kg Name of the input Quantity


In Kg 8-Chloro-11H-dienzo[b,f]thiepine-10-one

8.00 Zotepine 10.00

2-(Chloro ethyl) di methyl amine hydrochloride

4.50 Toluene Recovery 320.00

Potassium carbonate 4.50 Toluene Loss 17.00 DMSO 240.00 Cyclo hexane Recovery 665.00 MIBK 700.00 Cyclo hexane Loss 35.00 Toluene 345.00 Ethanol Recovery 228.00 Cylcohexane 700.00 Ethanol Loss 12.00 Ethanol 240.00 MIBK Recovery 665.00 Activated carbon 2.00 MIBK Loss 35.00 Water 100.00 Effluent water 107.38 (Water-100,Generated water-

0.55,Potassium chloride-4.58, Toluene-2,Potassium carbonate-0.25)

Spent carbon 2.00 DMSO Recovery 240.00 Process Emission 1.35 (Carbon dioxide) Organic Residue 6.27 (Organic Impurities-0.27,Toluene-

6)

Total 2344.00 Total 2344.00



24. ZOPICLONE


Stage-1

6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7-dihydro-pyrrolo[3,4-b]pyrazin-5-one product

reacts with N-Methyl piperazine and Triphogene in MDC in the presence of

Potassium carbonate in MDC to give Zopiclone as product.



ZOPICLONE

Route of Synthesis:

Stage-1

N

N

N

O

OH

N

Cl

6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7-dihydro-pyrrolo[3,4-b]pyrazin-5-one

C11H7ClN4O2

262.65

+

N-Methyl piperazine

N NH

C5H12N2

100.16

+

Triphosgene

Cl

ClCl

O

O

OCl

ClCl

C3Cl6O3

296.75/3=98.91

+ K2CO3

Potassium carbonate

138.20

MDC

N

N

N

O

NCl

N

O

NCH3

+ CO2

O

Zopiclone (Pure)

C17H17ClN6O3

388.81

44.0

+ 2 KCl

2X74.55=149.10

+ H2O

18.0

1/3



ZOPICLONE

Flow Chart:

Stage-3MDC RecMTBE Rec

6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7-dihydro-pyrrolo[3,4-b]pyrazin-5-oneN-Methyl piperazineTriphosgenePotassium carbonateMDCMTBE

ZOPICLONE



ZOPICLONE

Material Balance:

Material balance of Zopiclone Stage-1



In Kg 6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7- dihydro-pyrrolo[3,4-b]pyrazin-5-one

31.00 Zopiclone 45.00

N-Methyl piperazine 11.82 MDC Recovery 3325.00 Triphosgene 11.70 MDC Loss 175.00 Potassium carbonate 16.50 MTBE Recovery 184.00 Tetra butyl ammonium bromide 1.00 MTBE Loss 9.00 MDC 3510.00 Effluent water 520.72 MTBE 193.00 (Water-500,Generated water-

2.12,Potassium chloride-17.6, Tetra butyl ammonium bromide-1)

Activated carbon 1.50 Spent carbon 1.50 Water 500.00 Process Emission 5.19 (Carbon dioxide) Organic Residue 11.11 (Organic impurities-1.11,MDC-10) Total 4276.52 Total 4276.52



25. DEFERASIROX


Stage-1

4-Amino benzoic acid reacts with Sodium nitrite in the presence of Sulfuric acid and

forms diazonium salt and it is reduced with Sodium sulphite and hydrolysed with

Hydrochloric acid to give stage-1 as product.

Stage-2

Stage-1 reacts with sodium acetate in water media to give stage-2 as product.

Stage-3

Salicylic acid reacts with salicylic amide and Thionyl chloride in the presence of

O-Xylene as a solvent media to give stage-3 as product.

Stage-4

Stage-3 reacts with stage-2 in the presence of Methanol as a solvent media to give

stage-4 as product.

Stage-5

Stage-4 undergoes recystallisation using Methanol to give Deferasirox (pharma) as

product.



DEFERASIROX

Route of synthesis:

Stage-1:

HOOC

NH2

4-Amino-benzoic acid

C7H7NO2

137.13

+ NaNO2 + Na2SO3

126.04

+ 4 HCl

4X36.45=145.8068.99Sodium nitrite Sodium sulphite Hydrochloric acid

HOOC

NHNH2.HCl

4-Hydrazino-benzoic acid hydrochlorideC7H9ClN2O2

188.61

+

64.06Sulphurdioxide

+ NaCl +

58.44

H2O

18.00Sodium chloride

SO22 NaOCl +

2X74.44=148.88

Sodium hypochlorite

Sulfuric acid



Stage-2:

HOOC

NHNH2.HCl

4-Hydrazino-benzoic acid hydrochlorideC7H9ClN2O2

188.61

+

Sodium acetate

H3C

O

ONa

C2H3NaO2

82.03

HOOC

NHNH2

4-Hydrazino-benzoic acid

C7H8N2O2

152.15

+

Acetic acid

H3C

O

OH

60.05

+ NaCl

Sodium chloride

58.44

Water



Stage-3:

+OH

COOH

+ SOCl2

2-Hydroxy-benzoic acid

OH

O

NH2

2-Hydroxy-benzamide

C7H7NO2

137.13

C7H6O3

138.12

Thionyl chloride

118.97

Methanol

N

O

O

HO

2-(2-Hydroxy-phenyl)-benzo[e][1,3]oxazin-4-one

C14H9NO3

239.22

+ 2HCl + SO2 + H2O

2X36.5=73.00

Hydrochloric acid Sulphur dioxide64.06

18.00



Stage-4:

N

O

O

HO

2-(2-Hydroxy-phenyl)-benzo[e][1,3]oxazin-4-one

C14H9NO3

239.22

+ NH

COOH

H2N

4-Hydrazino-benzoic acid

C7H8N2O2

152.15

N

N N

OH

COOH

HO

Deferasirox(crude)

C21H15N3O4

373.36

+ H2O

18.00

Methanol



Stage-5:

N

N N

OH

COOH

HO

Deferasirox(crude)

C21H15N3O4

373.36

MethanolN

N N

OH

COOH

HO

Deferasirox(pure)C21H15N3O4

373.36

Purification



DEFERASIROX

Flow Chart:

Stage-1

4-Aminobenzoic acidSodium nitriteSulphuric acidHydrochloric acid

Sodium chlorideGenerated water

Stage-2Stage-1Sodium acetateWater

Sodium chlorideEffluent water

Stage-3

Salicylic acidSalicylamideThionyl chlorideMethanol

Hydrochloric acidSulphur dioxideMethanol Rec

Stage-4

Stage-34-Hydrazino benzoicacidMethanol

Methanol RecGenerated water

Stage-5Stage-4MethanolActivated carbon

Methanol Rec

DEFERASIROX



DEFERASIROX

Material Balance:

Material Balance of Deferasirox Stage-1



in Kg 4-Amino benzoic acid 35.00 Stage-1 29.00 Sodium nitrite 11.00 Effluent water 135.53 Sodium sulfite 19.50 (Water-100,Generated water-2.75,

Sodium chloride-9.3,Sodium hypochlorite-23.48)

Hydrochloric acid 23.00 Process Emission 9.90 Water 100.00 (Sulphur dioxide) Organic Residue 14.07 Total 188.50 Total 188.50




in Kg Stage-1 29.00 Stage-2 23.00

Sodium acetate 13.00 Effluent water 218.49 Water 200.00 (Water-200,Acetic acid-9.51,

Sodium chloride-8.98)

Organic Residue 0.51 Total 242.00 Total 242.00






in Kg Salicylic acid 21.00 Stage-3 35.00 Thionyl chloride 19.00 Toluene Recovery 283.00 Salicylamide 21.00 Toluene Loss 15.00 Toluene 300.00 Methanol Recovery 234.50 Methanol 250.00 Methanol Loss 12.50 Water 150.00 Effluent water 166.38 (Water-150,Generated water-2.73,

Hydrochloric acid-11.65,Methanol-1,Toluene-1)

Process Emission 10.22 (Sulphur dioxide)

Organic Residue 4.40 (Organic impurities-1.4,Methanol-

2,Toluene-1)





in Kg Stage-3 35.00 Stage-4 54.00 Stage-2 23.00 Methanol Recovery 233.50 Methanol 250.00 Methanol Loss 12.50 Generated water 2.63 Organic Residue 5.37 (Organic impurities-1.37,

Methanol-4)




Material Balance of Deferasirox Stage-5(pharma)

Batch Size:50.0Kgs Name of the input Quantity


in Kg Stage-4 54.00 Deferasirox 50.00 Methanol 200.00 Methanol Recovery 185.00 Activated carbon 1.00 Methanol Loss 10.00 Spent carbon 1.00 Organic Residue 9.00 (Organic impurities-4,Methanol-5) Total 255.00 Total 255.00



26. TAPENTADOL HYDROCHLORIDE


Stage-1

(2R, 3R)-3-(3-Methoxyphenyl)-2-methylpentyl) dimethyl amine reacts with

Hydrochloric acid and Sodium hydroxide in the presence of MDC as solvent media to

give stage-1 as product.

Stage-2

Stage-1 product reacts with Hydrochloric acid in the presence of acetone as solvent

media to give Tapentadol Hydrochloride as product.



TAPENTADOL HYDROCHLORIDE

Route of Synthesis:

Stage-1

N

OCH3

[3-(3-Methoxy-phenyl)-2-methyl-pentyl]-dimethyl-amine

C15H25NO

235.37

+ HCl

Hydrochloric acid

36.5

+ NaOH

Sodium Hydroxide

40.0

MDC

N

OH

3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol

C14H23NO

221.34

+ NaCl

58.5

+ CH3OH

Methanol

32.04Sodium chloride



Stage-2

N

OH

3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol

C14H23NO

221.34

+HCl

Hydrochloric acid

36.5

Acetone

N

OH

HCl

Tapentadol Hydrochloride

C14H24ClNO

257.84




Flow Chart:

2R, 3R)-3-(3-Methoxyphenyl)-2-methylpentyl) di methyl amineHydrochloric acidSodium hydroxideMDC

Stage-1 MDC Rec

Stage-2 Acetone Rec

Stage-1Hydrochloric acidAcetone





Material Balance:

Material Balance of Tapentadol Hydrochloride Stage-1



in Kg 2R, 3R)-3-(3-Methoxyphenyl)-2-methylpentyl) di methyl amine

108.00 Stage-1 92.00

Hydrochloric acid 16.00 MDC Recovery 130.50

Sodium hydroxide 17.00 MDC Loss 7.50 MDC 150.00 Effluent water 538.20 Water 500.00 (Water-500,Sodium chloride-24.86,

Methanol-13.34)

Organic Residue 22.80 (Organic impurities-10.8,MDC-12) Total 791.00 Total 791.00

Material Balance of Tapentadol Hydrochloride Stage-2



in Kg Stage-1 92.00 Tapentadol Hydrochloride 100.00 Hydrochloric acid 16.00 Acetone Recovery 45.50

Acetone 50.00 Acetone Loss 2.50 Activated carbon 5.00 Organic Residue 10.00 (Organic impurities-8,Acetone-2) Spent carbon 5.00 Total 163.00 Total 163.00



27. THALIDOMIDE


Stage-1

2-(2,6-Dihydro tetrahydro pyran-3-yl) isoindole-1,3-dione reacts with urea in the

presence of Ethanol as solvent media to give Thalidomide as product.

.

THALIDOMIDE

Route of Synthesis:

Stage-1:

N

O

O

O

O

O

2-(2,6-Dioxo-tetrahydro-pyran-3-yl)-isoindole-1,3-dione

C13H9NO5

259.21

+ H2N NH2

O

Urea

CH4N2O

60.06

EtOHN

O

O

NH

O

O

Thalidomide

C13H10N2O4

258.23

+ NH3 + CO2

17.0 44.0



THALIDOMIDE

Flow Chart:

Stage-1

THALIDOMIDE

Pthalyl Glutamic acid UreaEthanolN,N-Dimethyl formamide

Ethanol Rec

THALIDOMIDE

Material Balance:

Material Balance of Thalidomide Stage-1



in Kg Pthalyl Glutamic acid 116.00 Thalidomide 100.00

Urea 25.00 N,N-Dimethyl formamide Recovery

87.00

N,N-Dimethyl formamide 100.00 N,N-Dimethyl formamide Loss 10.00 Sodium carbonate 20.00 Effluent water 729.00

Activated carbon 5.00 (Water-700,Ammonia-7,Sodium carbonate-20,DMF-2)

Water 700.00 Process Emissions 27.30

(Carbon dioxide-19.7,Ammonia-7.6)

Spent carbon 5.00 Organic Residue 7.70 (Organic impurities-6.7,DMF-1) Total 966.00 Total 966.00



28. TOFISOPAM


Stage – 1

3-[2-3(3,4-Dimethoxy benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-one is react with hydrazine in the presence of Methanol as solvent media to give Tofisopam(crude) as product.

Stage – 2

Tofisopam crude undergoes purification with Methanol as solvent media to give Tofisopam (pure) as product.



TOFISOPAM

Route of Synthesis:

Stage-1:

O

CH3

CH3

O

OCH3

OCH3

H3CO

H3CO

H3CO

OCH3

+ NH2-NH2N

N

C2H5CH3

H3CO

OCH3

3-[2-(3,4-Dimethoxy-benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-one

C22H26O6

386.44

Hydrazine

32.05

Tofisopam(Crude)

C22H26N2O4

382.45

+ 2H2O

2X18=36.0

Stage-2:

H3CO

OCH3

NN

C2H5CH3

H3CO

OCH3

Tofisopam(Crude)C22H26N2O4

382.45

MethanolH3CO

OCH3

NN

C2H5CH3

H3CO

OCH3

Tofisopam(pure)

C22H26N2O4

382.45



TOFISOPAM

Flowchart:

Stage-1

Stage-2

TOFISOPAM

3-[2-(3,4-Dimethoxy-benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-oneHydrazine hydrateMethanolAcetic acidAmmonia

Methanol Rec

Stage-1�Methanol

Methanol Rec



TOFISOPAM

Material Balance:

Material Balance of Tofisopam Stage-1



in Kg 3-[2-(3,4-Dimethoxy-benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-one

37.00 Stage-1 22.00

Hydrazine hydrate 3.00 Methanol Recovery 87.00 Methanol 100.00 Methanol Loss 10.00 Acetic acid 5.00 Effluent water 208.32 Water 200.00 (Water-200,Generated water-

2.32, Acetic acid-5,Methanol-1)

Organic Residue 17.68 (Organic impurities-15.68,

Methanol-2)


Material Balance of Tofisopam Stage-2



in Kg Stage-1 22.00 Tofisopam 20.00 Methanol 50.00 Methanol Recovery 47.00 Activated carbon 2.00 Methanol Loss 2.50 Spent carbon 2.00 Organic Residue 2.50 (Organic impurities-2,Methanol-

0.5)




Annexure - IV

WATER CONSUMPTION DETAILS

S. No Purpose Water

Requirement in KLD

1 Process 190.00 2 Washings 25.00 3 Boiler Make up 153.00 4 Cooling towers Make up 289.00 5 DM Plant 25.00 6 Scrubbing system 10.00 7 Domestic Usage 25.00 8 Gardening 40.00 Total 757.00



Annexure - V

WASTE WATER DETAILS

S. No Purpose Effluent In KLD

1 Process 198.00 2 Washings 25.00 3 Boiler Blow down 22.00 4 Cooling towers Blow down 29.00 5 DM Plant Regeneration 25.00 6 Scrubbing system 10.00 7 Domestic 20.00 Total 329.00

HTDS & LTDS DETAILS

S. No Purpose HTDS in KLD

LTDS in KLD

Effluent in KLD Disposal Method

1 Process 197.00 1.00 198.00 HTDS Effluent sent to Stripper followed by MEE/ATFD system.

LTDS effluents along with MEE condensate treated in ETP.

Treated effluent sent to RO, to recover RO permeates water for reuse.

RO rejects sent to MEE followed by ATFD. MEE/ATFD condensate collected for reuse/recycle.

ATFD salts sent to TSDF

2 Washings 0.00 25.00 25.00 3 Boiler Blow down 22.00 0.00 22.00

4 Cooling towers Blow down

0.00 29.00 29.00

5 RO/ DM Plant 25.00 0.00 25.00

6 Scrubbing system 10.00 0.00 10.00

7 Domestic 0.00 20.00 20.00 Sent to STP Total 254.00 75.00 329.00



Annexure - VI

HAZARDOUS WASTE & SOLID WASTE DETAILS WITH MODE OF DISPOSAL

S. No Name of the Hazardous Waste

Quantity Kg/Day Mode of Disposal

1

Organic waste (Process residue-4336 Solvent Distillation Residue -1020)

5356.00 Sent to Cement Industries

2 Spent Carbon 863.00 Sent to Cement Industries 3 Inorganic Waste 780.00 Sent to TSDF 4 MEE Salts 7213.00 Sent to TSDF 5 ETP Sludge 3000.00 Sent to TSDF

6 Stripper Distillate 3.00 KLD Sent to Cement Industries / TSDF.

7 STP Sludge 20.00 Used as a manure

8 Used Oils 15 KL / Annum

SPCB Authorized Agencies for Reprocessing / Recycling

9 Detoxified Containers 2000 Nos / Month

After Detoxification sold to SPCB Authorized buyers

10 Mixed Spent Solvents 3070.00

Kgs / Day Disposed to SPCB Authorized parties.

11 Used Lead Acid Batteries 6 Nos / Annum Buyback for new Batteries.

Solid Waste Details

12 Coal ash from boiler 30550.00 Disposed to Brick Manufacturers



Annexure - VII

STACK EMISSION DETAILS FOR PROPOSED BOILERS

Particulars Units

2X10.0 TPH Coal fired

Boiler (Proposed)

4.0 TPH Coal fired Boiler (Proposed)

2.0TPH Coal

fired Boiler (Existing)

Type of Fuel -- Indian Coal Indian Coal Indian Coal Coal Consumption TPD 25.0 10.0 5.0 Ash Content % 47 47 47 Sulphur Content % 0.8 0.8 0.8 Nitrogen Content % 1.07 1.07 1.07 No. of Stacks No 1 1 1.0 Height of the Stack m 32 32 30 Diameter of Stack m 0.80 0.60 1.0 Temperature of Flue Gas oC 140 120 110 Velocity of Flue Gas m/s 8.50 9.0 9.5 Particulate Matter at outlet of Bag filter (Based on 115 mg/Nm3 at outlet)

gm/sec 0.73 0.39 0.276

Sulphur dioxide emission (Based on 200 mg/Nm3 at outlet)

gm/sec 1.27 0.67 0.48

Oxides of Nitrogen emission (Based on 400 mg/Nm3 at outlet)

gm/sec 2.54 1.34 0.96

The Industry will kept 10.0TPH Coal fired boiler as Standby.

STACK EMISSION DETAILS FOR PROPOSED DG SETS

Capacity In KVA

Emission of SPM

in mg/Nm3

Emission Of SO2 in mg/Nm3

Emission of NOx

in mg/Nm3

Stack dia. In m

Flue Gas

Temp. in OC

Stack Height in m

Flue gas Velocity In m/sec.

3X500 KVA (Proposed)

80.0 190.0 235.0 0.30 130 10 15.0

3X1000 KVA (Proposed)

90.0 200.0 320.0 0.30 140 11 22.0



STACK EMISSIONS FOR THERMOPACK BOILER

Particulars Units Thermic fluid

Heater (Existing)

Thermic fluid Heater

(Proposed)

Thermo pack Boiler Capacity K. Cal/Hr. 1,00,000 X 1 No 5,00,000 X 2 Nos

Type of Fuel -- Diesel Diesel

Stack Height m 11.02 13.56

Stack dia m 0.2 0.3

Stack Temperature oC 100 120

Flue gas velocity m/sec 9.0 8.5

Efficiency % 85.0 85.0

Fuel Consumption per Day Liters / Day 220 1100

Particulate Matter at outlet of

Bag filter (Based on 115

mg/Nm3 at outlet)

g/sec 0.043 0.091



Annexure - VIII

PROCESS EMISSION DETAILS

POLLUTING PROCESS EMISSION DETAILS:

S. No Name of the Gas Quantity

in Kgs/Day Treatment Method

1 Sulfur dioxide 256.00 Scrubbed by using C. S. Lye solution

NON- POLLUTING PROCESS EMISSION DETAILS:

S. No Name of the Gas Quantity

in Kgs/Day Treatment Method

1 Carbon dioxide 143.00 Dispersed into atmosphere

2 Hydrogen 4.00

Diffused by using Nitrogen through Flame arrestor



Annexure - IX

LIST OF RAW MATERIALS

1. AMISULPRIDE

S. No Raw Material Used in Kgs/Batch

Used in Kgs/Day Source

1 2-Methoxy-4-amino-5-ethyl sulphonyl benzoic acid

141.00 70.50 Indigenous

2 1-Ethyl-2-amino methyl pyrrolidine


3 Ethyl chloro formate 59.00 29.50 Indigenous 4 Triethylamine 80.00 40.00 Indigenous 5 Sodium hydroxide 145.00 72.50 Indigenous 6 Acetone 630.00 315.00 Indigenous 7 Isopropyl alcohol 150.00 75.00 Indigenous 8 Activated carbon 9.00 4.50 Indigenous



2. CARBIDOPA

S. No Raw Material Used in

Kgs/Batch

Used in

Kgs/Day

Source

1 Methyl Dopa 40.00 320.00 Indigenous

2 Methanol 302.35 2418.80 Indigenous

3 Thionyl Chloride 22.53 180.24 Indigenous

4 Caustic Soda Flakes 15.50 124.00 Indigenous

5 Cyclohexanone 20.00 160.00 Indigenous

6 Toluene 320.00 2560.00 Indigenous

7 Liquid Ammonia 10.5 84.00 Indigenous

8 Sodium Hypochlorite 15.00 120.00 Indigenous

9 Conc. Hydrochloric Acid 42 336.00 Indigenous

10 Boric Acid 7.25 58.00 Indigenous

11 Chloroform 187.50 1500.00 Indigenous

12 Sodium metabisulphite 0.55 4.40 Indigenous

13 Hydrochloric Acid 7.00 56.00 Indigenous

14 Ammonium hydroxide 5.00 40.00 Indigenous

15 Sodium meta bisulphate 0.87 6.96 Indigenous

16 Acetone 1.64 13.12 Indigenous

17 Activated Carbon 5.00 40.00 Indigenous



3. CARVEDILOL


Kgs/Batch

Used in

Kgs/Day Source

1 4(Oxiranyl methoxy)-9H-Carbazole


2 (2-methoxyphenoxy)ethylamine 35.00 1272.73 Indigenous

3 Ethyl acetate 438.00 15927.29 Indigenous


5 Activated carbon 2.00 72.73 Indigenous



4. CARVEDILOL PHOSPHATE

S.No Raw Material Used in

Kgs/Batch

Used in

Kgs/Day Source

1 Carvedilol 47.00 205.28 Indigenous

2 Phosphoric acid 12.00 52.41 Indigenous




5. CINITAPRIDE HYDROGEN TARTRATE


Kgs/Batch

Used in

Kgs/Day

Source

1 4-Amino-2-ethoxy-5nitro-N-(4-piperidyl)benzamide


2 3-Cyclohexene-1-methanol 7.10 42.60 Indigenous

3 Benzene sulfonyl chloride 11.17 67.02 Indigenous

4 Sodium carbonate 3.35 20.10 Indigenous

5 TEA 24.60 147.60 Indigenous

6 Tartaric acid 15.20 91.20 Indigenous

7 Cyclohexane 88.20 529.20 Indigenous

8 DMF 198.00 1188.00 Indigenous





6. DEFERASIROX


Kgs/Batch

Used in

Kgs/Day

Source

1 4-Amino benzoic acid 35.00 163.33 Indigenous

2 Sodium nitrite 11.00 51.33 Indigenous

3 Sodium sulfite 19.50 91.00 Indigenous

4 Hydrochloric acid 23.00 107.33 Indigenous

5 Sodium acetate 13.00 60.67 Indigenous

6 Salicylic acid 21.00 98.00 Indigenous

7 Thionyl chloride 19.00 88.67 Indigenous

8 Salicylamide 21.00 98.00 Indigenous






7. DAPOXETINE HYDROCHLORIDE


Kgs/Batch

Used in

Kgs/Day

Source

1 (S)-3-Chloro-1-phenyl propan-1-ol reacts


2 1-Napthol 34.00 42.50 Indigenous

3 Dimethylamine 33.00 41.25 Indigenous

4 IsopropanolHCl 55.00 68.75 Indigenous

5 Dimethyl sulfoxide 280.00 350.00 Indigenous

6 Sodium chloride 34.00 42.50 Indigenous

7 Mesyl chloride 50.00 62.50 Indigenous

8 Triethylamine 126.00 157.50 Indigenous

9 N,N-Dimethyl amino pyridine 0.02 0.03 Indigenous






8. EPALRESTAT


Kgs/Batch

Used in

Kgs/Day

Source

1 3-carboxy methyl rhodanine


2 2-Methyl cinnamldehdye 55.00 137.50 Indigenous

3 Sodium acetate 78.00 195.00 Indigenous

4 Acetic acid 797.00 1992.50 Indigenous

5 DMF 2981.00 7452.50 Indigenous




9. ESZOPICLONE


Used in Kgs/Day

Source

1 O-Phenylene diamine 24.20 12.10 Indigenous 2 Glyoxal 7.60 3.80 Indigenous 3 Potassium permanganate 158.00 79.00 Indigenous 4 Toluene 230.00 115.00 Indigenous 5 Hydrochloric acid 60.00 30.00 Indigenous 6 Sodium bisulfate 35.00 17.50 Indigenous 7 Ethylene chloride 44.00 22.00 Indigenous 8 Acetic anhydride 168.00 84.00 Indigenous 9 Sodium chloride 11.50 5.75

10 Hyflow 2.50 1.25 Indigenous 11 2-Amino-5-Chloropyridine 16.90 8.45 Indigenous 12 Sodium boro hydride 6.00 3.00 Indigenous 13 Acetic acid 1.60 0.80 14 Acetonitrile 225.00 112.50 Indigenous 15 Toluene 160.00 80.00 Indigenous 16 Chloroform 1530.00 765.00 Indigenous 17 1,4-Dioxane 30.00 15.00 Indigenous 18 Activated carbon 6.00 3.00 Indigenous 19 N-Methyl piperazine 26.00 13.00 Indigenous 20 Triphosgene 26.00 13.00 Indigenous 21 Potassium carbonate 83.00 41.50 Indigenous 22 Tetrabutyl ammonium

bromide 1.00

0.50 Indigenous

23 1,4-Toluyl tartaric acid monohydrate

45.00 22.50

Indigenous

24 Sodium hydroxide 45.00 22.50 Indigenous 25 Methylene chloride 3510.00 1755.00 Indigenous 26 Methyl tertiary butyl ketone 193.00 96.50 Indigenous 27 Methanol 428.00 214.00 Indigenous 28 Acetone 820.00 410.00 Indigenous 29 Isopropyl alcohol 160.00 80.00 Indigenous



10. FLUCONAZOLE

S. No

Raw Material Used in Kgs/Batch

Used in Kgs/Day

Source

1 1[2-(2,4-Difluorophenyl)-2,3-epoxy propyl)-1H-1,2,4-Triazole

77.45

464.70

Indigenous

2 1,2,4-Triazole 45.10 270.60 Indigenous

3 Sodium sulphate 130.00 780.00 Indigenous






11. IRON SUCROSE

S. No


Used in Kgs/Day

Source

1 Ferric Chloride 93.71 624.73 Indigenous


3 Sucrose 45.00 300.00 Indigenous

4 Sodium hydroxide 5.00 33.33 Indigenous



12. ITOPRIDE HYDROCHLORIDE


Used in Kgs/Day

Source

1 3,4-Dimethoxybenzoic acid 47.90 206.02 Indigenous

2 Thionyl chloride 28.01 120.47 Indigenous

3 4-(N,N-di methyl amino ethoxy)benzyl amine



5 IPA.HCl 94.00 404.29 Indigenous


7 Chloroform 449.00 1931.15 Indigenous

8 IPA 943.00 4055.84 Indigenous



11 Aq.ammonia 159.00 683.85 Indigenous



13. KETOROLAC TROMETHAMINE


Used in Kgs/Day

Source

1 Ketorolac 79.86 620.27 Indigenous

2 Tromethamine 33.14 257.40 Indigenous






14. LEVOCETIRIZINE HYDROCHLORIDE


Used in Kgs/Day

Source

1 1-[((4-Chlorophenyl)phenyl)methyl]-4-[(phenylsulphonyl)]piperazine

46.20

55.44

Indigenous

2 2(2-Chloroethoxy )acetamide 14.90 17.88 Indigenous

3 4-Hydroxy benzoic acid 16.00 19.20 Indigenous

4 Hydrobromic acid 8.80 10.56 Indigenous




8 Potassium iodide 1.70 2.04 Indigenous


10 MDC 1860.00 2232.00 Indigenous





15. LEVOSULPRIDE

S. No


Used in Kgs/Day

Source

1 Methyl-2-methoxy-5-sulfamoyl benzoate


2 1-Ethyl-2-amino methyl pyrrolidine


3 Ethylene glycol 290.00 2772.013 Indigenous





16. LINEZOLID

S. No


Used in Kgs/Day

Source

1 N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl aniline


2 Carbonyl di imidazole 41.25 1069.45 Indigenous

3 Hydrazine Hydrate 13.35 346.11 Indigenous

4 Acetic anhydride 27.23 705.96 Indigenous


6 MDC 2707.00 70181.68 Indigenous






17. MOSAPRIDE CITRATE DIHYDRATE

S. No


Used in Kgs/Day

Source

1 2-Amino methyl-4-(4-fluorobenzyl)morpholine


2 4-Amino-5-chloro-2-ethoxy benzoic acid


3 Citric acid 22.16 118.19 Indigenous

4 Ethyl chloro formate 19.00 101.33 Indigenous

5 TEA 33.00 176.00 Indigenous

6 MDC 1865.00 9946.67 Indigenous



9 Activated Carbon 16.00 85.33 Indigenous



18. ONDANSETRON HYDROCHLORIDE DIHYDRATE


Used in Kgs/Day

Source

1 3-Dimethylamino methyl-9-methyl-1,2,3,9-tetrahydro carbazole-4-one

10.50

70.00

Indigenous

2 2-Methyl imidazole 4.00 26.67 Indigenous






19. PREGABALIN

S. No


Used in Kgs/Day

Source

1 3-(Amino methyl)-5-methyl hexanoic acid


2 Mandelic acid 129.10 905.98 Indigenous

3 Liq. Ammonia 14.60 102.46 Indigenous

4 Citric acid monohydrate 74.60 523.52 Indigenous





20. RACECADOTRIL


Used in Kgs/Day

Source

1 2-Benzylacryloyl chloride 58.00 193.33 Indigenous

2 Glycine benzyl ester-p-tosylate


3 Thioacetic acid 30.00 100.00 Indigenous

4 Triethylamine 100.00 333.33 Indigenous

5 Sodium bicarbonate 16.00 53.33 Indigenous


7 Isopropyl alcohol 1130.00 3766.67 Indigenous

8 n-Hexane 480.00 1600.00 Indigenous






21. TAMSULOSIN HYDROCHLORIDE

S. No


Used in Kgs/Day

Source

1 (R)-5-[[2-(2-Ethoxy phenoxy) ethyl)amino]propyl]-2-methoxy benzene 19.30

331.32

Indigenous

2 Hydrochloric acid 13.30

228.32 Indigenous

3 Methanol 190.00

3261.67 Indigenous

4 Acetone 310.00

5321.67 Indigenous



22. TAPENTADOL HYDROCHLORIDE


Used in Kgs/Day

Source

1 2R, 3R)-3-(3-Methoxyphenyl)-2-methylpentyl) di methyl amine

108.00

720.00

Indigenous








\

23. TIZANIDINE HYDROCHLORIDE

S. No


Used in Kgs/Day

Source

1 5-chloro-2,1,3-benzo-thiadiazole-4-ylamine


2 1-Acetyl-imidazolidin-2-one 78.20 5.11 Indigenous 3 Phosphorous oxy chloride 94.00 6.14 Indigenous 4 Sodium hydroxide 188.00 12.28 Indigenous 5 Methanol 5530.00 361.29 Indigenous 6 Activated carbon 30.00 1.96 Indigenous 7 Hydrochloric acid 23.00 1.50 Indigenous 8 Sodium sulphate 98.00 6.40 Indigenous 9 Acetic acid 31.00 2.03 Indigenous



24. THALIDOMIDE


Kgs/Batch Used in Kgs/Day

Source

1 Pthalyl Glutamic acid 116.00 319.00 Indigenous

2 Urea 25.00 68.75 Indigenous

3 N,N-Dimethyl formamide 100.00 275.00 Indigenous





25. TOPIRAMATE


Used in Kgs/Day

Source

1 D-Fructose 50.00 200.00 Indigenous



4 Isopropyl alcohol 12.00 48.00 Indigenous

5 n-Hexane 83.00 332.00 Indigenous

6 Sulfuryl chloride 53.00 212.00 Indigenous

7 Ammonia 3.26 13.04 Indigenous


10 Pyridine 34.00 136.00 Indigenous






17 IPA 115.00 460.00 Indigenous

18 Activated carbon 4.00 16.00



26 TOFISOPAM



Source

1 3-[2-(3,4-Dimethoxy-benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-one

37.00

740.00

Indigenous

2 Hydrazine hydrate 3.00 60.00 Indigenous


4 Acetic acid 5.00 100.00 Indigenous




27. ZOPICLONE



Source

1 6-(5-Chloro-pyridin-2-yl)-7-hydroxy-6,7- dihydro-pyrrolo[3,4-b]pyrazin-5-one

31.00

236.52

Indigenous

2 N-Methyl piperazine 11.82 90.18 Indigenous

3 Triphosgene 11.70 89.27 Indigenous

4 Potassium carbonate 16.50 125.89 Indigenous

5 Tetra butyl ammonium bromide


6 MDC 3510.00 26780.13 Indigenous

7 MTBE 193.00 1472.53 Indigenous




28. ZOTEPINE



Source

1 8-Chloro-11H-dienzo[b,f]thiepine-10-one


2 2-(Chloro ethyl) di methyl amine hydrochloride


3 Potassium carbonate 4.50 90.00 Indigenous

4 DMSO 240.00 4800.00 Indigenous

5 MIBK 700.00 14000.00 Indigenous


7 Cylcohexane 700.00 14000.00 Indigenous

8 Ethanol 240.00 4800.00 Indigenous




Solvents Details Annexure - X

S. No Product Name Production Capacity Kg/Month

Solvent Name

Quantities in Kg/Day

Solvent Input

Solvent Loss

Solvent Recovery

Mixed Spent

Solvents Input

Mixed Spent

Solvents recovery

Solvent in waste water

Solvent in

Residue

1 Amisulpride 3000.00 Acetone 315.00 15.75 298.50 0.00 0.00 0.50 0.25

Isopropyl alcohol 75.00 3.75 71.25 0.00 0.00 0.00 0.00

Total 390.00 19.50 369.75 0.00 0.00 0.50 0.25

2 Carbidopa 6000.00 Methanol 2258.80 80.00 2080.00 0.00 0.00 68.88 0.00

Chloroform 1500.00 76.00 1424.00 0.00 0.00 0.00 0.00

Total 3758.80 156.00 3504.00 0.00 0.00 68.88 0.00

3 Carvedilol 60000.00 Ethyl acetate 15018.18 727.27 14290.91 1818.18 1800.00 0.00 0.00

Methanol 14363.65 690.91 13672.74 0.00 0.00 0.00 0.00

Total 29381.83 1418.18 27963.65 1818.18 1800.00 0.00 0.00

4 Carvedilol Phosphate 7600.00 Acetone 1729.66 82.99 1642.30 0.00 0.00 4.37 0.00

Total 1729.66 82.99 1642.30 0.00 0.00 4.37 0.00

5 Cinitapride HydrogenTartrate

6300.00 Cyclohexane 529.20 24.00 505.20 0.00 0.00 0.00 0.00

DMF 1188.00 54.00 1134.00 0.00 0.00 0.00 0.00

Methanol 1398.00 66.00 1332.00 0.00 0.00 0.00 0.00

Total 3115.20 144.00 2971.20 0.00 0.00 0.00 0.00

6 Dapoxetine Hydrochloride

3000.00 Methanol 1243.75 49.75 1190.25 0.00 0.00 2.50 1.25

Ethyl acetate 1756.25 87.81 1668.44 0.00 0.00 0.00 0.00



Total 3000.00 137.56 2858.69 0.00 0.00 2.50 1.25

7 Epalrestat 9000.00 Acetic acid 1992.50 97.50 1895.00 0.00 0.00 0.00 0.00

DMF 7452.50 372.50 7002.50 0.00 0.00 2.50 75.00

Total 9445.00 470.00 8897.50 0.00 0.00 2.50 75.00

8 Eszopiclone 150.00 Toluene 195.00 7.80 182.20 0.00 0.00 1.00 5.00

Ethylene chloride 22.00 1.10 20.90 0.00 0.00 0.00 0.00

Acetonitrile 112.50 5.63 106.88 0.00 0.00 0.00 0.00

Chloroform 765.00 38.25 726.75 0.00 0.00 0.00 0.00

1,4-Dioxane 15.00 0.65 14.40 0.00 0.00 0.00 0.00

Methanol 214.00 8.56 205.44 0.00 0.00 0.50 0.00

Acetone 410.00 20.50 389.50 0.00 0.00 1.00 0.00

MDC 1755.00 87.75 1652.25 0.00 0.00 0.00 15.00

Isopropyl alcohol 80.00 3.20 76.80 0.00 0.00 0.00 0.00

Total 3568.50 173.44 3375.12 0.00 0.00 2.50 20.00

9 Fluconazole 18000.00 Acetone 3780.00 180.00 3600.00 0.00 0.00 0.00 0.00

Ethyl acetate 6456.00 318.00 6078.00 0.00 0.00 0.00 60.00

Total 10236.00 498.00 9678.00 0.00 0.00 0.00 60.00

10 Iron Sucrose 20000.00 No Solvent 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Total 0.00 0.00 0.00 0.00 0.00 0.00 0.00

11 Itopride Hydrochloride 12000.00 Toluene 6356.99 313.98 5995.70 0.00 0.00 4.30 43.01

Chloroform 1931.15 94.62 1836.53 0.00 0.00 0.00 0.00

IPA 4055.84 202.15 4206.38 0.00 0.00 0.00 0.00



Methanol 2176.31 107.53 2068.78 0.00 0.00 0.00 0.00

Total 14520.29 718.27 14107.38 0.00 0.00 4.30 43.01

12 Ketorolac tromethamine 24000.00 Methanol 2058.25 100.97 1949.51 0.00 0.00 7.77 0.00

Acetone 17693.23 869.90 16660.22 0.00 0.00 7.77 155.34

Total 19751.48 970.87 18609.73 0.00 0.00 15.53 155.34

13 Levocetirizine Dihydrochloride

1800.00 Toluene 1818.00 90.00 1728.00 0.00 0.00 1.20 0.00

MDC 2232.00 111.60 2108.40 0.00 0.00 0.00 12.00

Acetone 558.00 27.60 530.40 0.00 0.00 0.00 0.00

Total 4608.00 229.20 4366.80 0.00 0.00 1.20 12.00

14 Levosulpride 39000.00 Ethylene glycol 2772.06 133.82 2638.24 0.00 0.00 0.00 0.00

Methanol 18161.47 908.07 17375.17 0.00 0.00 0.00 0.00

Total 20933.53 1041.90 20013.41 0.00 0.00 0.00 0.00

15 Linezolid 70000.00 Methanol 19522.22 959.26 18537.04 1296.30 1270.37 25.93 0.00

MDC 69533.53 3474.08 65774.26 0.00 0.00 0.00 285.19

Ethyl acetate 20870.43 1037.04 19833.39 0.00 0.00 0.00 0.00

Acetone 40133.45 1996.30 38137.15 0.00 0.00 0.00 0.00

Total 150059.63 7466.69 142281.84 1296.30 1270.37 25.93 285.19

16 Mosapride citrate dihydrate 12000.00 MDC 9946.67 496.00 9397.33 0.00 0.00 0.00 53.33

Acetone 1253.33 58.67 1194.67 0.00 0.00 0.00 0.00

Methanol 1120.00 53.33 1061.33 0.00 0.00 5.33 0.00

Total 12320.00 608.00 11653.33 0.00 0.00 5.33 53.33



17 Ondansetron Hydrochloride Dihydrate

3000.00 Methanol 480.00 20.00 453.33 0.00 0.00 6.67 0.00

Total 480.00 20.00 453.33 0.00 0.00 6.67 0.00

18 Pregabalin 20000.00 Methanol 10273.68 512.28 9754.39 0.00 0.00 7.02 0.00

Total 10273.68 512.28 9754.39 0.00 0.00 7.02 0.00

19 Racecadotril 8000.00 Isopropyl alcohol 3766.67 188.33 3545.00 0.00 0.00 0.00 33.33

n-Hexane 1600.00 64.00 1532.67 0.00 0.00 0.00 3.33

Toluene 1266.67 50.67 1216.00 0.00 0.00 3.33 0.00

Methanol 3433.33 171.67 3261.67 0.00 0.00 6.67 0.00

Total 10066.67 474.67 9555.33 0.00 0.00 10.00 36.67

20 Tamsulosin Hydrochloride 10300.00 Methanol 3261.67 130.47 3096.87 0.00 0.00 17.17 34.33

Acetone 5321.67 266.08 5055.58 0.00 0.00 17.17 0.00

Total 8583.33 396.55 8152.45 0.00 0.00 34.33 34.33

21 Tizianidine Hydrochloride 300.00 Methanol 1106.00 49.20 938.40 0.00 0.00 0.40 0.00

Total 1106.00 49.20 938.40 0.00 0.00 0.40 0.00

22 Topiramate 3000.00 Isopropyl alcohol 48.00 4.00 44.00 0.00 0.00 0.00 0.00

n-Hexane 332.00 16.00 316.00 0.00 0.00 0.00 0.00

MDC 2660.00 132.00 2520.00 0.00 0.00 0.00 8.00

Toluene 6960.00 348.00 6608.00 0.00 0.00 4.00 0.00

Ethyl acetate 1080.00 56.00 1024.00 0.00 0.00 0.00 0.00

IPA 460.00 24.00 432.00 0.00 0.00 4.00 0.00

Total 11540.00 580.00 10944.00 0.00 0.00 8.00 8.00



23 Zopiclone 10300.00 MTBE 1472.52 68.67 1403.85 0.00 0.00 0.00 0.00

MDC 26780.13 1335.19 25368.64 0.00 0.00 0.00 76.30

Total 28252.65 1403.86 26772.49 0.00 0.00 0.00 76.30

24 Zotepine 6000.00 MIBK 14000.00 700.00 13300.00 0.00 0.00 0.00 0.00

Toluene 6900.00 340.00 6520.00 0.00 0.00 40.00 0.00

Cylco hexane 14000.00 700.00 13300.00 0.00 0.00 0.00 0.00

Ethanol 4800.00 240.00 4560.00 0.00 0.00 0.00 0.00

Total 39700.00 1980.00 37680.00 0.00 0.00 40.00 0.00

25 Defasirox 7000.00 Toluene 1400.00 1320.67 70.00 0.00 0.00 4.67 4.67

Methanol 3266.67 3047.33 163.33 0.00 0.00 0.00 56.00

Total 4666.67 4368.00 233.33 0.00 0.00 4.67 60.67

26 Tapentadol Hydrochloride

20000.00 MDC 1000.00 870.00 50.00 0.00 0.00 0.00 80.00

Acetone 333.33 303.33 16.67 0.00 0.00 0.00 13.33

Total 1333.33 1173.33 66.67 0.00 0.00 0.00 93.33

27 Thalidomide 8250.00 N,N-Dimethyl formamide 275.00 239.25 27.50 0.00 0.00 5.50 2.75

Total 333.33 290.00 33.33 0.00 0.00 6.67 3.33

28 Tofisopam 12000.00 Methanol 3000.00 2680.00 250.00 0.00 0.00 20.00 50.00

Total of all products 400000.00 100.00 89.33 8.33 0.00 0.00 0.67 1.67

Solvents Grand Total of all products 403253.57 25471.82 376884.74 3114.48 3070.37 251.97 1019.67

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