Method of preparing phosphodiesterase IV inhibitors

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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546330, 546331, 546332, 546335, 546337, 546338, 546339, 546340, 546342, C07D21330

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058080821

ABSTRACT:
A process for the preparation of Phosphodiesterase IV inhibitors is described. The process consists of eight chemical steps involving five isolations to prepare the title compound from readily available isovanillin in 35% overall yield (Scheme 1). The process is highlighted by: a) a highly diastereoselective Michael addition of phenyllithium using (1R, 2S) cis-aminoindanol as a chiral auxiliary, b) highly crystalline intermediates providing for efficient purifications, c) crystallization of the final compound as its CSA salt for excellent enantiomeric purity.

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