Facile conversion of racemic ibuprofen to (S)-ibuprofen

The methyl ester of ibuprofen was quantitatively formed by Fischer esterification and converted into (S)-ibuprofen in 94% yield with an ee of 94% under dynamic kinetic resolution conditions at pH 9.8, using Candida rugosa lipase, and 20% DMSO. The (R)-methyl ibuprofen ester was observed to racemize by chiral HPLC without the Candida rugosa lipase present. The rates of in situ racemization and enzymatic hydrolysis for the dynamic kinetic resolution were determined to be 0.026 +/- 0.004 and 0.053 +/- 0.004 h(-1), respectively. The rate of enzymatic hydrolysis when no DMSO was present was twice as fast but no racemization occurred. A facile purification of enriched (S)-ibuprofen was developed. Overall, 88% of racemic ibuprofen by weight was converted into (S)-ibuprofen with an ee of 99.7%. (C) 2012 Elsevier Ltd. All rights reserved.