Review of Continuous Process for Modafinil

9/17/09

REVIEW OF CONTINUOUS PROCESS FOR MODAFINIL

Profitability through Simplicity

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BATCH  CONTINUOUS

Profitability through Simplicity

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Profitability through Simplicity

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BATCH vs. CONTINUOUS

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QBD FEASIBLE ONLY IF :

WE “DO NOT” HAVE COMPLETE COMMAND OF THE CHEMISTRY AND THE PROCESS.

CHALLENGE. CAN BE DONE. Profitability through Simplicity

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9/17/09

ELEMENTS OF QBD •  PHYSICAL PROPERTIES •  REACTION MECHANISM •  CHEMISTRY THEY ARE AN ALLY AND FACILITATOR. Profitability through Simplicity

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Profitability through Simplicity

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Profitability through Simplicity

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UNDERSTAND AND MANIPULATE

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PHYSICAL PROPERTIES:

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Profitability through Simplicity

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9/17/09

APPLICATION OF MY DO’S FOR MODAFINIL PROCESS QUALITY PRODUCT FIRST TIME AND ALWAYS.

BETTER BATCH OR A CONTINUOUS PROCESS Profitability through Simplicity

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“CHEMISTRY-CENTRIC” TRADITIONS

USP 6,875,893 & 7,057,069 7,244,865 AND OTHER PATENTS

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BENZHYDROL + THIOUREA+ HBr  S-BENZHYDRYLTHIOURONIUM BROMIDE + H2O

SOLVENT BASED PROCESSES. BENZHYLDRYTHIOL + KBr + UREA + CHLOROACETAMIDE + ALKALI

NEED TO LOOK AT ALTERNATES.

2-(BENZHYDRYLTHIOL) ACETAMIDE + KCl 2-(BENZHYLDRYLSULFINYL) ACETAMIDE [MODAFINIL]

Profitability through Simplicity

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Profitability through Simplicity

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Profitability through Simplicity

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STEP # 1: Benzhydrol + HBr  Bromodiphenyl methane + H2O + Thiourea S-benzhydrylthiouronium bromide + H2O

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9/17/09

STEP # 1 REACTION MECHANISM SECOND POSSIBLE MECHANISM

Profitability through Simplicity

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Profitability through Simplicity

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# 1 MECHANISM (1) MORE LIKELY BASED ON PHYSICAL PROPERTIES AND REACTION MECHANISM, THERE ARE OPPORTUNITIES TO MANIPULATE REACTANTS AND THE PROCESS.

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CHEMICAL

PHYSICAL STATE

MP°C

BENZHYDROL

SOLID

69

THIOUREA

SOLID

181

HBr

LIQUID

KOH/K2CO3

LIQUID/SOLID

CHLOROACETAMIDE

SOLID

ACETIC ACID

LIQUID

H2O2

LIQUID

SOLUBILITY

WATER WATER

118

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WATER

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BENZHYDROL FEED: CHEMICAL

PHYSICAL STATE MP°C LIQUID

•  PATENTS SUGGEST USE AS A SOLUTION.

SOLID

•  BASED ON MY EXPERIENCE:

SOLID SOLID

110

SOLID

164

PROPERTIES SUGGEST: BENZHYDROL MELT AS A POSSIBILITY.

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Profitability through Simplicity

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9/17/09

RATIONALE FOR USE OF MELT

RATIONALE FOR USE OF MELT

HIGH PRODUCTIVITY & YIELD

HIGH PRODUCTIVITY & YIELD

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Profitability through Simplicity

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MODAFINIL STOICHIOMETRY

STEPS 2 TO 4

EXAMPLE: Theoretical

Suggested

BENZHYDROL

1.0

1.0

THIOUREA

1.0

1.2

HBr

1.0

1.2

KOH

1.0

1.2

CHLOROACETAMIDE

1.0

2.88

ACETIC ACID

1.0

3.2

H2O2

1.0

2.0

Profitability through Simplicity

CAN BE RATIONALIZED SIMILARLY AND SIMPLIFIED. A SOLVENT WITH LOW WATER SOLUBILITY AND AZEOTROPE, CAN FACILITATE THE PROCESS AND COULD BE USED.

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Profitability through Simplicity

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Profitability through Simplicity

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COMMERCIAL CONTINUOUS PROCESS Benzhydrol, HBr & Thiourea Storage tanks Chloroacetamide And Alkali storage tanks

Rx

Rx Purification & Crystallization

Acetic acid Hydrogen peroxide Storage tanks

Profitability through Simplicity

Rx

Rx

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9/17/09

QBD ELEMENTS DELIVER: SMOOTH, SAFE, CONTROLLED AND A COMPLAINT PROCESS.

THANK YOU VERY MUCH.

Girish MALHOTRA, PE President EPCOT INTERNATIONAL 29150 Bryce Road Pepper Pike, OH 44124 (216)-292-0626 (216)-591-0932 Website:

QBA Profitability through Simplicity

Blog:

QBD EPCOT International

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