An efficient procedure for the resolution of α-cyano-α-fluoro- p-tolylacetic acid (CFTA) via the diastereomeric N-carbobenzyloxy-cis-1-amino-2- indanol esters

Development of a new, efficient resolution method of α-cyano-α- fluoro-p-tolylacetic acid (CFTA) 2a has been successfully achieved, which has been troublesome to obtain by conventional methods, in spite of its outstanding ability as an NMR chiral derivatizing agent. Fractional recrystallization of a mixture of the diastereomeric CFTA esters prepared from racemic CFTA chloride and (1R,2S)-N-carbobenzyloxy-cis-1-amino-2-indanol (-)-B afforded the less-soluble diastereomer, which was hydrolyzed to give (S)-2a. It has also been demonstrated that optically active N-acetyl-cis-1-amino-2-indanol is effective for the chromatographic resolution of α-arylacetic acids including ibuprofen and naproxen.