Synthesis of a key intermediate, (S)-2-[(3-hydroxypropyl)sulfinyl]-1-(o-tolyl)imidazole, for the platelet aggregation inhibitor, OPC-29030 via lipase-catalyzed enantioselective transesterification

Optically active 2-[(3-hydroxypropyl)sulfinyl]-1-(o-tolyl) (S)-2 was synthesized by kinetic resolution of (+/-)-2 with lipase and hydrolysis of the acetate (S)-3 with potassium carbonate. The reaction mixture of the lipase-catalyzed transesterification was converted to the phthalic acid derivative (R)-4, and this (R)-4 and the unreacted acetate (S)-3 were fractionated without use of column chromatography. The unrequired recovered alcohol (R)-2 was also racemized and (+/-)-2 was repeatedly submitted to the lipase-catalyzed transesterification. (C) 1997 Elsevier Science Ltd.