A process for producing enantiomerically enriched
(S)-.alpha.-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5
(4H)-acetic acid hydrocarbyl ester, represented by the formula:
##STR1##
Is provided, wherein R.sup.1 and R.sup.2 are hydrogens and R.sup.3 is
methyl (i.e., (S)-Clopidogrel). The process includes the steps of: (a)
contacting
N-2-chlorobenz-aldehyde-ylidene-1-ethylamine-2(2-thiophenyl)imine and an
HCN source, in the presence of a non-metallic asymmetric Strecker catalyst
to form enantiomerically enriched
(S)-.alpha.,.alpha.-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile;
(b) contacting the enantiomerically enriched
(S)-.alpha.,.alpha.-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile
and a formaldehyde equivalent, in the presence of an acid catalyst to form
enantiomerically enriched
.alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile;
and (c) contacting the enantiomerically enriched
.alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile
and a reagent capable of converting a cyano group into an ester group to
form enantiomerically enriched hydrocarbyl ester of
(S)-.alpha.-(2-chlorophenyl)-6,7-dihydrothieno-[3,2-c]pyridine-5(4H)-aceti
c acid.
Um processo para produzir enriquecido enantiomerically (S)-.alpha.-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5 (ester ácido do hydrocarbyl 4H)-acetic, representado pela fórmula: ## do ## STR1 É fornecido, wherein R.sup.1 e R.sup.2 são hydrogens e R.sup.3 é methyl (isto é, (S)-Clopidogrel). O processo inclui as etapas de: (a) N-2-chlorobenz-aldehyde-ylidene-1-ethylamine-2(2-thiophenyl)imine contatando e uma fonte do HCN, na presença de um catalizador asymmetric não metálico de Strecker a dar forma enantiomerically enriqueceram (S)-.alpha..alpha.-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile; (b) contatando enriquecido enantiomerically (S)-.alpha..alpha.-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile e um equivalente do formaldehyde, na presença de um catalizador ácido a dar forma enantiomerically enriqueceu o alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile; e (c) contatar o alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-alpha.-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile enantiomerically enriquecido e um reagent capazes de converter um grupo cyano em um grupo do ester ao formulário enriqueceu enantiomerically o ester do hydrocarbyl de (ácido de S)-.alpha.-(2-chlorophenyl)-6,7-dihydrothieno-[3,2-c]pyridine-5(4H)-aceti c.
