A scalable and expedient method of preparing diastereomerically and enantiomerically enriched pseudonorephedrine from norephedrine

Norephedrine has been efficiently converted into the corresponding diastereomer pseudonorephedrine using a three step, one-pot reaction. The three step process involves treatment of norephedrine with di-tert-butyl dicarbonate (Boc2O); cyclization by way of mesylate formation at the alcohol; and lithium hydroxide mediated hydrolysis of the oxazolidinone. The diastereomeric purity was determined by HPLC and the enantiomeric purity was determined by optical activity measurements and chiral stationary phase HPLC analysis of the pseudonorephedrine oxazolidinone derivatives.

Figure optionsDownload as PowerPoint slide

(1S,2S)-2-Amino-1-phenyl-1-propanolC9H13NO[α]D28=+31.8 (c 3.49, EtOH)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1S,2S)

(4S,5S)-4-Methyl-5-phenyl-2-oxazolidinoneC10H11NO2[α]D29=+21.6 (c 2.3, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1S,2S)

(1R,2R)-2-Amino-1-phenyl-1-propanolC9H13NO[α]D28=-31.4 (c 3.49, EtOH)Source of chirality: (1S,2R)-norephedrineAbsolute configuration: (1R,2R)