PROCESS FOR SYNTHESIS OF SYN AZIDO EPOXIDE AND ITS USE AS INTERMEDIATE FOR THE SYNTHESIS OF AMPRENAVIR & SAQUINAVIR

摘要

Disclosed herein is a novel route of synthesis of syn azide epoxide of formula 5, which is used as a common intermediate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir and Palinavir obtained by Cobalt-catalyzed hydrolytic kinetic resolution of racemic anti-(2SR,3SR)-3-azido-4-phenyl-1,2-epoxybutane (azido-epoxide).;

主权项

1. An enantioselective synthesis of syn azido epoxide of formula (+)-5 comprising: wherein, ‘A’ is substituted or unsubstituted aryl group, wherein substituents are selected from (C1-C8) alkyl, aryl, arylalkyl, halo, (C1-C8) alkoxy, i) subjecting allylic alcohol to epoxidation with m-chloroperbenzoic acid (mCPBA) to obtain racemic epoxy alcohol; ii) ring opening of epoxide with azide anion in presence of Lewis acid to produce the corresponding anti-azido alcohol, followed by selective tosylation of primary alcohol to afford tosylate; iii) treating tosylate with base to obtain racemic azido epoxide; and iv) subjecting racemic azido epoxide to hydrolytic kinetic resolution to obtain corresponding 1,2-diol and syn azido epoxide followed by isolating syn azido epoxide with enantiomeric purity >98%.