Organocatalytic Chiral Synthesis of Centrally Acting Muscle Relaxant (S)-Mephenesin

Abstract

Chiral synthesis of centrally acting muscle relaxant (S)-mephenesin was achieved using L-proline catalyzed α-aminoxylation of 3-(2-methyl-phenxoy)propanal as chirality induction step. The chiral synthesis started with commercially available 2-cresol and was accomplished in four steps with overall yield 56%. The enantiomeric excess of final product (S)-mephenesin is >98%. The chiral purity was determined by chiral-HPLC using Chiralcel-OD column. The synthesis involves oxidation of primary alcohol to aldehyde with iodoxybenzoic acid (IBX) as one of the steps.