Zentiva K.s.

Zentiva, A.s.

Hana Stepankova

Josef Hajicek

Jan Kalivoda

Miroslav Veverka

Stefan Vodny

Eva Veverkova

Stanislav Simek

Gregor Sedmak

Racemization of the R(&#x2212;) isomer of the (2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (Formula II) (also called R clopidogrel) is performed via conversion of a portion thereof to the S(+)isomer and it takes place in an organic solvent selected from alcohols, esters, ketones or ethers, or in their mixtures, in the presence of a base selected from substances of formula R1R2R3R4N+OH&#x2033; wherein R1, R2, R3 and R4 are identical or different substituents selected from C1-C5 alkyls or C5, C6 cycloalkyls or aryls, C7-C9 alkyl-cycloalkyls or alkyl-aryls, the molar ratio of the base to the starting substance being 1:1 to 1:10., OMe Cl I Cl&#x3c;VOMe II. 

Method of racemization of the R(&#x2212;) isomer of the (2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester

A method for manufacturing hydrogen sulphate (alpha S) of the alpha-(2-chlorophenyl)-6,7dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (clopidogrel hydrogen sulphate) of formula I, in crystalline Form I, wherein the compound of formula is separated out of a solution of clopidogrel in the form of the free base or salt in a solvent selected from the series of primary, secondary or tertiary C1-C5 alcohols, their esters with C1-C4 carboxylic acids, or optionally of mixtures thereof. 

Method for manufacturing crystalline form I of clopidogrel hydrogen sulphate

The compound of formula (III), optionally its alkaline salt, is reacted with a compound of formula VII, wherein X is a leaving group, resulting in (S)-rivastigmine of formula II, which is then optionally converted into (S)-rivastigmine hydrogentartrade of formula I. 

Method of production of (&#x2212;)-(S)-3-[1-(dimethylamino)ethyl]phenyl-N-ethyl-N-methylcarbamate

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Cesky Brod, Czechia

Hana Stepankova