Enantioselective esterification of racemic ketoprofen in non-aqueous solvent under reduced pressure

The enantioselective esterification of (R,S)-ketoprofen catalyzed by Candida antarctica lipase (type B) has been performed with dodecanol in solvent media under reduced pressure. The nature of the solvent, either aromatic, ether or ketone, affects the activity of the lipase and its enantioselectivity, defined as the ratio of the initial rates of reaction for each enantiomer. Faster reactions are obtained in hydrophobic solvents whereas the enantioselectivity remains constant across all solvents, except for ketones where the enantioselectivity increases with a decrease of the Log P. When the same reaction is performed with 1-propanol in xylenes, an inhibition by the nucleophile is observed, which is not detected when using dodecanol under the same conditions.