A three-component synthesis of aminomethylenebis-H-phosphinates

Aminomethylenebisphosphonic acids display a number of interesting biological activities. Although the structural optimization of amine substituents has been widely studied, potential modifications of the phosphonate groups remain virtually unexplored. Thus, a two-stage procedure for the synthesis of aminomethylenebis-H-phosphinates is developed. The three-component condensation of an amine, triethyl orthoformate, and ethyl diethoxymethyl-H-phosphinate and the subsequent hydrolysis are crucial steps in this synthetic pathway.