Direct chromatographic resolution and isolation of the four stereoisomers of meta-hydroxyphenylpropanolamine.
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%.
Van Dort
M E
ME
Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0552, USA. mvandort@umich.edu
D002852:Chromatography, Ion Exchange; D008401:Gas Chromatography-Mass Spectrometry; D008680:Metaraminol; D011412:Propanolamines / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism
D011412:Propanolamines; D008680:Metaraminol