Resolution of racemic flurbiprofen by lipase-mediated esterification in organic solvent

Article abstract of DOI:10.1016/0957-4166(95)00223-C

Resolution of rac-flurbiprofen, 2-fluoro-α-methyl-[1,1'-biphenyl]-4-acetic acid (1), by biocatalytic methodologies has been studied. Enzymatic hydrolysis of rac-flurbiprofen methyl ester (2) in aqueous-organic medium gave poor results. Transesterification of the same ester mediated by immobilized lipase from Candida antarctica (Novozym 435) in organic solvent proceeded with good enantiomeric excess but the isolation of the product required chromographic separation and therefore was unsuitable for large scale preparation. Direct esterification of 1 with methanol in acetronitrile promoted by Novozym 435 proved to be the best method since it gave, via a twofold kinetic resolution, S-flurbiprofen with excellent enantiomeric excess. The R-flurbiprofen methyl ester formed in the reaction can be converted into the starting rac-flurbiprofen by alkaline hydrolysis or, alternatively, into R-flurbiprofen by hydrolysis with acid.