L. V. Langen, A. F. V. Rantwijk, R. Sheldon
Sep 12, 2003
Citations
0
Influential Citations
60
Citations
Journal
Organic Process Research & Development
Abstract
The asymmetric synthesis of (R)-o-chloromandelic acid, a key intermediate for the anti-thrombotic agent clopidogrel, via the almond meal catalyzed hydrocyanation of 2-chlorobenzaldehyde and subsequent acidic hydrolysis was developed into an industrially viable procedure. The use of a minimum amount of water consistent with enzyme activity and a slow feed of the reactants were the keys to obtaining (R)-2-chloromandelonitrile in a high (98%) yield and satisfactory (90%) enantiomeric excess. Acidic hydrolysis of the nitrile followed by crystallization from toluene afforded enantiopure (ee > 99%) (R)-2-chloromandelic acid.