SYNTHESIS AND RESOLUTION OF THE NOVEL APPETITE-SUPPRESSANT 2-BENZYLMORPHOLINE, A NONSTIMULANT ISOMER OF PHENMETRAZINE

Abstract— The synthesis of 2‐benzylmorpholine from allylbenzene together with its resolution into its (+)‐and (—)‐enantiomers is reported. Oral dosing of the racemate to dogs caused appetite suppression with an ED50 of 3 and 5.5 rag kg−1 at I and 2 h, respectively, after access to a meat meal. No stimulant activity was observed in dogs given oral doses of 200 mg kg−1 but the appetite suppressant effect in dogs declined during 20 days of chronic oral dosing at 10 mg kg−1. Appetite suppression activity was shown to reside in the (+)‐enantiomer. 1990 Royal Pharmaceutical Society of Great Britain