A Scalable Asymmetric Synthesis of (R)-2-Amino-1-(3-pyridinyl)ethanol Dihydrochloride via an Oxazaborolidine Catalyzed Borane Reduction

Abstract

This report describes a scalable process for the asymmetric synthesis of (R)-2-amino-1-(3-pyridinyl)ethanol dihydrochloride. The stereochemistry of the product is set via a reduction of 3-chloroacetyl pyridine with 2 equiv of borane-dimethyl sulfide and a catalytic amount of an in situ generated oxazaborolidine. The enantiomeric excess (ee) of the reductive step depends on the addition rate of the substrate and the temperature. The authors hypothesize that the low ee observed during a fast addition of the substrate or at low temperatures is due to the slow regeneration of the active catalyst from the catalyst−product complex.