PREPARATION OF AMINOALKYL CHLOROHYDRIN HYDROCHLORIDES - KEY BUILDING-BLOCKS FOR HYDROXYETHYLAMINE-BASED HIV PROTEASE INHIBITORS

Enantiomerically pure N,N-dibenzyl-alpha-amino aldehydes reacted with (chloromethyl)lithium, generated in situ from bromochloromethane and l ithium metal, to give predominantly erythro aminoalkyl epoxides. Treat ment of the crude epoxides with aqueous hydrochloric acid gave crystal line (2S,3S)-N,N-dibenzylamino chlorohydrin hydrochlorides in 32-56% o verall yield and high isomeric purity. These compounds are versatile s ynthetic intermediates for the preparation of hydroxyethylamine-based HN protease inhibitors, either directly as such, or via conversion to the corresponding N-Boc-(2S,3S)-aminoalkyl epoxides. The processes des cribed do not make use of hazardous reagents or intermediates, do not require chromatographic purifications, and are thus amenable to the pr eparation of large quantities of these versatile building blocks.