The synthesis of the disodium salt of fenidronate by the reaction of benzoic acid with phosphorus trichloride and phosphorous acid in methanesulfonic acid was investigated and optimized. It was enough to use 3.2 equivalents of phosphorus trichloride and there was no need to apply phosphorous acid. Both the one-step and two-step versions led to similar results giving the product in ca. 45% yield and in high purity. It was also possible to start directly from benzoyl chloride or ethyl benzoate. The work-up included in all cases hydrolysis and pH adjustment followed by purification. The fenidronic acid standard that was necessary for the analysis of our samples was prepared by another approach, by the addition of dimethyl phosphite to the carbonyl group of the -oxophosphonate, followed by hydrolysis of the tetramethyl ester so formed.
Keywords: Dronic acid, dronate, synthesis, intermediate, optimization, titration.