Enzymatic esterification of racemic ibuprofen catalyzed by Candida rugosa lipase in cyclohexane at 40 ºC was developed with high selectivity for (S)-ibuprofen over the (R)-ibuprofen enantiomer. The length of the alcohol used changed the velocity of the esterification from 48 hours for decal-1-ol to 96 hours for butan-1-ol. Esterification with decan-1-ol was more enantioselective than that of butan-1-ol as measured by their respective enantiomeric ratios, E, 130 and 46.

Bulb to bulb distillation of (R)-ibuprofen and decan-1-ol from the (S)-decyl ibuprofen ester, besides not requiring solvents, was run at a larger scale than chromatography. Bulb to bulb separation of ibuprofen from the butyl ibuprofen was not effective because of the close boiling points of carboxylic acid and ester. As expected total hydrolysis of (S)-ibuprofen esters in the native solvent of lipase, water, was possible although the reaction of the decyl ibuprofen ester was half as slow (48 hours) as the reaction of the butyl ibuprofen ester probably because of the lower solubility of the decyl ester in water. Nevertheless the combined time of esterification and hydrolysis of decyl and butyl ibuprofen esters was comparable.

Chiral HPLC analysis demonstrates that pure (S)-ibuprofen was isolated, without racemization, by enzymatic esterification of racemic ibuprofen with decan-1-ol, effective and efficient bulb to bulb distillation and separation of products, and environmentally benign hydrolysis of the (S)-decyl ibuprofen ester with the same Candida rugosa lipase