A simple synthesis of monofluoromethylene bisphosphonic acid

Article abstract of DOI:10.1016/0022-328X(88)80556-4

A simple synthesis of monofluoromethylene bisphosphonic acid has been devised, starting with an Arbusov reaction between fluorotribromomethane and triisopropyl phosphite to give diisopropyl dibromofluoromethylphosphonate.A Michaelis-Becker reaction between the latter and an excess of the sodium salt of diisopropyl phosphite yields tetraisopropyl bromofluoromethylene bisphosphonate, which is not isolated but undergoes nucleophilic debromination and protonation during the reaction and subsequent work up to produce tetraisopropyl monofluoromethylene bisphosphonate.De-esterification of the tetraester with bromotrimethylsilane followed by hydrolysis and cation exchange chromatography gives di(triethylammonium)monofluoromethylene bisphosphonate, which is converted into the free acid by further ion exchange chromatography.