[DIFLUORO(PYRIDINYL)METHYL]PHOSPHONATES

Abstract

An efficient and convenient method for the synthesis of all isomeric [difluoro(pyridinyl)methyl]phosphonates based on electrophilic fluorination of the corresponding (pyridinylmethyl)phosphonates with N-fluorobenzenesulfonimide has been developed. Hydrolysis and subsequent catalytic hydrogenation of the obtained [difluoro(pyridinyl)methyl]phosphonates afford the respective piperidine-containing α-, β-, and γ-aminophosphonic acids. Thermally unstable diethyl [difluoro(pyridin-4-yl)methyl]phosphonate undergoes O–N transfer of ethyl group to give the corresponding betaine. Hydrolysis of the latter affords 4-[difluoro(phosphono)methyl]-1-ethylpyridin-1-ium salt.