An Efficient Chiral Moderator Prepared from Inexpensive (+)-3-Carene: Synthesis of the HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor DPC 963

Abstract

The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.