METHOD OF MAKING (1S, 4R)-1-AZABICYCLO[2.2.1]HEPTAN-3-ONE AND (1R, 4S), 1-AZABICYCLO[2.2.1]HEPTAN-3-ONE

摘要

Racemic (+/-)-1-azabicyclo[2.2.1]heptan-3-one may be efficiently resolved into its (1S, 4R)- and (1R, 4S)-1-azabicyclo[2.2.1]heptan-3-one isomers by formation of di-p-toluoyl hemitartrate salts by combination with di-p-toluoyl-L-tartaric acid and di-p-toluoyl-D-tartaric acid, respectively. Selective crystallization using one of the di-p-toluoyltartaric acids in less that stoichiometric amount in a suitable solvent mixture allows isolation of the desired isomer as its respective di-p-toluoyl hemitartrate in high isomeric purity. The isolated hemitartrates are storage stable and may be used as such in the preparation of pharmaceuticals and other biologically active compounds, or may be used to provide the free base of the respective 1-azabicyclo[2.2.1]heptan-3-one isomer.