Diastereomeric Resolution of Racemic o-Chloromandelic Acid.

ABSTRACT The separation of rac-o-chloromandelic acid 1 with enantiopure aryloxypropylamine via diastereomeric salt formation was investigated. ( R)- o-chloromandelic acid ( R)- 1, a key intermediate for the antithrombotic agent clopidogrel, was obtained in 65% yield and 98% ee by Dutch resolution of rac- 1 with ( S)-2-hydroxyl-3-( p-chlorophenoxy) propylamine ( S)- 5 as resolving agent and ( S)-2-hydroxyl-3-( o-nitrophenoxy) propylamine ( S)- 4 as nucleation inhibitor. Chirality 24:1013-1017, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]