R. Morrone et al., RESOLUTION OF RACEMIC FLURBIPROFEN BY LIPASE-MEDIATED ESTERIFICATION IN ORGANIC-SOLVENT, Tetrahedron : asymmetry, 6(7), 1995, pp. 1773-1778
Resolution of rac-flurbiprofen, 2-fluoro-alpha-methyl-[1.1'-biphenyl]-
4-acetic acid (1), by biocatalytic methodologies has been studied. Enz
ymatic hydrolysis of rac-flurbiprofen methyl eater (2) in aqueous-orga
nic medium gave poor results. Transesterification of the same eater me
diated by immobilized lipase from Candida antarctica (Novozym(R) 435)
in organic solvent proceeded with good enantiomeric excess but the iso
lation of the product required chromatographic separation and therefor
e was unsuitable for large scale preparation. Direct esterification of
1 with methanol in acetonitrile promoted by Novozym(R) 435 proved to
be the best method since it gave, via a twofold kinetic resolution, S-
flurbiprofen with excellent enantiomeric excess. The R-flurbiprofen me
thyl eater formed in the reaction can be converted into the starting r
ac-flurbiprofen by alkaline hydrolysis or, alternatively, into R-flurb
iprofen by hydrolysis with acid.