Preparation of antithrombotic agent clopidogrel by a stereospecific route from a sulfonyloxy acetic ester

摘要

Preparation of clopidogrel comprising using methyl (R)-2-(2-chlorophenyl)-2-acetate derivatives with sulfonyloxy group in the 2-position, is new. Preparation of clopidogrel of formula (IV) comprises reacting 4,5,6,7-tetrahydrothieno(3,2-c)pyridine in the form of a base or a salt with an (R)-sulfonyloxy acetate derivative of formula (I), optionally in the presence of a base and optionally in an aqueous solution. R1 = benzyl, 1-4C alkyl (optionally substituted by one or more halo) or phenyl (optionally substituted by one or more halo, 1-4C alkyl or nitro). Independent claims are also included for: (a) an alternative preparation of (IV) comprising: (i) reacting (I) with 2-(thien-2-yl)ethylamine optionally in an aqueous solution; (ii) reacting the resulting methyl (+)-(S)- alpha -(2-(thien-2-yl)ethylamino)- alpha -(2-chlorophenyl) acetate with a formylation agent and cyclizing in the presence of an acid. (b) the preparation of (I). (I) are claimed per se.