Synthesis of difluoromethylphosphonamidates by direct addition of amine

The one step synthesis of difluoromethylphosphonamidates from dialkylphosphonates is reported. The addition of lithiated amides onto dialkyl difluoromethylphosphonates afforded the corresponding phosphonamidates, as potential prodrug precursors. The remarkable high stability of these phosphonamidates in acidic medium was studied by 31P NMR.

Synthesis of phosphonamidates was realized in one step from difluoromethylphosphonate dialkyl ester.