Abstract

The optimized synthesis of benzidronate involves the reaction of phenylacetic acid with 3 equivalents of phosphorus trichloride and 1 equivalent of phosphorous acid in methanesulfonic acid at 85 °C followed by hydrolysis, pH adjustment and purifications. The positive effect of phosphorous acid on the yield is a novel observation and is probably limited to this model. The heap of our experimental data obtained by varying the molar equivalent quantities of the P-reagents (PCl₃ and P(OH)₃) and reacting also phenylacetic chloride and ethyl phenylacetate allowed us to draw conclusions on the possible intermediates.

Keywords: Benzidronate, intermediates, optimization, phosphorous acid, phosphorus trichloride.

Graphical Abstract