PROCESS FOR SYNTHESIS OF AZETIDINE AND NOVEL INTERMEDIATES THEREFOR

摘要

PROCESS FOR SYNTHESIS OF AZETIDINE AND NOVEL INTERMEDIATES THEREFOR A novel process is disclosed, for preparing azetidine and 2 or 3 methyl and ethyl azetidine free bases by reacting primary arylmethylamine having suitable bulk providing substituents attached to the methyl carbon and an appropriate propane derivative having leaving groups in the one and three positions in hot organic solvent containing a non-nucleophilic base and an amount of water sufficient to promote azetidine ring formation to give N-protected-azetidines and deprotecting by hydrogenolysis under acidic conditions to give an acid salt of the azetidines and thereafter flashing off vaporized azetidine from a hot, agitated strong base solution or slurry and condensing to give the liquid azetidine free bases. Also disclosed are novel intermediates of the formulae: and ¢wherein Ar is optionally substituted phenyl, biphenyl or naphthyl, R1 is alkyl, cycloalkyl or Ar, R is hydrogen, methyl or ethyl, X is a leaving group, and R3, R4 and R5 are hydrogen, methyl or ethyl, provided that only one of them may be other than hydrogen!. The desired azetidine and its methyl and ethyl derivatives are useful in the preparation of pharmaceutical agents.