The Application of HPLC Chiral Stationary Phases to Stereochemical Problems of Pharmaceutical Interest: A General Method for the Resolution of Enantiomeric Amines as β-Naphthylcarbamate Derivatives

Abstract

The enantiomers of primary, secondary and some tertiary amines are resolved as carbamate derivatives formed by reaction with β-naphthylchloroformate. The enantiomeric carbamates are resolved on a commercially available Pirkle-type HPLC chiral stationary phase (CSP), consisting of (R)-N-(3,5-dinitrobenzoyl)-phenylglycine covalently bonded to silica, by using a mobile phase consisting of mixtures of isopropanol in hexane. In this manner, 12 amines structurally related to amphetamine were resolved, including such pharmacologically important compounds as methamphetamine and pseudoephedrine, neither of which had been previously resolved on Pirkle-type CSPs. Reaction of the haloformate with phenolic amines may be controlled to give either mono- or bis-derivatives; both gave useful resolutions. Simple aliphatic amines such as sec-butylamine were also resolved. The order of elution of the carbamates was consistently R,S; this elution pattern is discussed in terms of specific interactions between the carbamate and the CSP.