Synthesis of enantiomerically pure desmethylzopiclone and determination ofits absolute configuration

Two synthetic methods have been established for the preparation of enantiom erically pure desmethylzopiclone, a metabolite of zopiclone. In Method A, ( S)-desmethylzopiclone was prepared by demethylation of (S)-zopiclone with l -chloroethyl chloroformate in high yield. Enantiomerically pure zopiclone ( >99% eel was obtained through a highly efficient resolution process in >36% overall yield. In Method B, racemic desmethylzopiclone was resolved with L -N-benzyloxycarbonyl phenylalanine (L-ZPA) followed by recrystallization in good yield. The absolute stereochemistry of the (+)-enantiomer was first d etermined to be the (S)-configuration by X-ray crystallography. (C) 2001 El sevier Science Ltd. All rights-reserved.