STEREOSELECTIVE SYNTHESES OF BOTH ENANTIOMERS OF KETOCONAZOLE FROM (R)-EPICHLOROHYDRIN AND (S)-EPICHLOROHYDRIN

Stereoselective syntheses of both enantiomers of ketoconazole (1) from commercially available (R)- or (S)-epichlorohydrin has been developed . The key-step of these syntheses involves the selective substitution of the methylene chlorine atom by benzoate on a mixture of (2S,4R)-14a and (2R,4R)-15a or of their enantiomers, followed by crystallization of the corresponding cis-benzoates, (2R,4R)-18 or (2S,4S)-18, from whi ch (+)- or (-)-1 were obtained as described for (+/-)-1. The ee's of ( +) and (-)-ketoconazole were determined by HPLC on the CSP Chiralcel O D-H.