A facile synthesis of azetidin-2-ylphosphonic acid and its 1-alkyl derivatives

Treatment of racemic diisopropyl [1,3-bis(mesyloxy)propyl] phosphonate with allyl-, benzyl-, 2-hydroxyethyl-, or propylamine gave the corresponding di isopropyl [(3-(alkylamino)1-(mesyloxy)propyl]phosphonates. Heating of their toluene solution with aqueous potassium carbonate effected a cyclization t o diisopropyl (1-alkylazetidin-2-yl)phosphonates. In the 1-benzyl- and [1-( 2-hydroxyethyl)azetidin-2-yl] phosphonate, the isopropyl ester groups were removed by treatment with bromotrimethylsilane which gave 1-benzyl- and [1- (2-hydroxyethyl)azetidin-2-yl]phospho acid. Following hydrogenolysis of the benzyl group afforded azetidin-2-ylphosphonic acid.