Direct chromatographic resolution and isolation of the four stereoisomers of meta -hydroxyphenylpropanolamine

Abstract

Methods for the direct chiral chromatographic separation of the four stereoisomers of meta -hydroxyphenylpropanolamine (MHPA) on an analytical and preparative scale are described. Separations were carried out on a Crownpak CR (+) chiral column with 113 mM aqueous perchloric acid as the mobile phase. Baseline resolution of the more retained (+)-stereoisomers (1S configuration) and partial resolution of the less retained (−)-stereoisomers (1R configuration) were obtained under these chromatographic conditions. Removal of the bulk of the (1R,2S)-stereoisomer (metaraminol) from the initial crude mixture by fractional crystallization as the (+)-bitartarate salt substantially improved the peak resolution factors (Rs) of the remaining three stereoisomers. Semipreparative chromatographic resolution of the latter isomeric mixture provided milligram quantities of each stereoisomer in >97% enantiomeric excess. Subsequent recrystallization of their bitartarate or fumarate salts gave enantiomeric purities >99%. Chirality 11:684–688, 1999. © 1999 Wiley-Liss, Inc.