Direct chromatographic resolution and isolation of the four stereoisomers ofmeta-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.

Chiral Separations

“…Crown ether-based CSPs, both commercially available and newly synthesized, continue to see use in the area of enantioseparations. Van Dort reported the direct enantioresolution of the four stereoisomers of m-hydroxyphenylpropanolamine on a Crownpak CR(+) column (138). The separation of hydrophobic amino compounds was investigated using a Crownpak CR(+) column with the addition of crown ether, cyclodextrins, cations, etc., to the mobile phase to create a dynamically coated CSP (139).…”