M.W.
van der Meijden, M. Leeman, E. Gelens, W.L. Noorduin, H. Meekes, W.J.P.
van Enckevort, B. Kaptein, E. Vlieg, R.M. Kellogg,
Attrition-enhanced
deracemization in the synthesis of clopidogrel – a practical
application of a new discovery,
Org. Process Research & Dev. 13
(2009) 1195-1198
Abstract:
The recently discovered technique of
deracemization by means of attrition-induced grinding of a solid
conglomerate in contact with a solution wherein racemization occurs has
been used with a derivative of 2-chlorophenyl glycine, the key chiral
component in the synthesis of Clopidogrel (Plavix). Deracemization of
the racemate proceeds to a single enantiomer and in essentially
absolute enantiomeric excess. Further conversion of enantiomerically
pure material to Clopidogrel was achieved in 88% yield.