CHEMOENZYMATIC SYNTHESIS OF (R)-(-ALPHA-(4-FLUOROPHENYL)-4-(2-PYRIMIDINYL PIPERAZINEBUTANOL) AND LPHA-(4-FLUOROPHENYL)-4-METHYL-1-PIPERIDINEBUTANOL AS POTENTIAL ANTIPSYCHOTIC AGENTS())

A chemoenzymatic straightforward synthesis of lpha-(4-fluorophenyl)-4- methyl-1-piperidinebutanol (2) and luorophenyl)-4-(2-pyrimidinyl)-1-pi perazinebutanol (3), two potential antipsychotic agents, has been deve loped by two different approaches involving lipase-mediated resolution of the racemic compounds or through asymmetrization of the precursor alcohol 4. A second enzymatic resolution followed by condensation of ( R)-4 with 4-methylpiperidine (6) or 1-(2-pyrimidinyl)piperazine (7) le ads to (R)-2 and (R)-3 in good chemical and excellent optical yields ( >99% ee). (C) 1997 Elsevier Science Ltd.