Journal of Organic Chemistry 2001-01-01

Preparation of Aminoalkyl Chlorohydrin Hydrochlorides: Key Building Blocks for Hydroxyethylamine-Based HIV Protease Inhibitors.

PierreL. Beaulieu, Dominik Wernic

Index: J. Org. Chem. 61 , 3635, (1996)

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Abstract

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