PROCESS FOR KEY INTERMEDIATES FOR HIV PROTEASE INHIBITORS

摘要

Disclosed herein is a stereospecific synthesis amenable to the large scale preparation of a hydrochloric acid addition salt of a chlorohydrin of the formula wherein R1 and R2 are amino protective groups and R3 is an amino acid side chain or a protected amino acid side chain. The synthesis involves reacting an aldehyde of the formula wherein R1, R2 and R3 are as defined hereinbefore with (chloromethyl)lithium at -20 .degree.C or below and contacting the resulting diastereoisomeric mixture of lithium alcoholates with aqueous hydrochloric acid to obtain a separable mixture of the hydrochloric acid addition salts of the chlorohydrin and its corresponding hydroxy diastereoisomer. The hydrochloric acid addition salt of the chlorohydrin is transformed readily into corresponding optionally amino-protected aminoepoxides; for example, 3(S) (tert-butyloxycarbonylamino)-1,2(S)-epoxy-4-phenyl-butane.