Dávid Illés Nagy

Optimized Synthesis of Etidronate

The synthesis of Etidronate (as the disodium salt) by the reaction of acetic acid with phosphorus trichloride/ phosphorus acid in methanesulfonic acid was studied and optimized. We showed that it is enough to use 3.2 equivalents of the phosphorus trichloride and there is no need to apply phosphorus acid. In the two-step variation of the synthesis, the acetyl chloride was formed by the reaction of acetic acid with phosphorus trichloride, thionyl chloride or triphosgene, then the intermediate was converted to etidronate by reaction with 2.2 equivalents of phosphorus trichloride. The work-up included in all cases hydrolysis and pH adjustment.

Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents

The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the heterogeneity of the reaction mixtures. This review sheds light on the optimum choice and ratio of the P-reactants, and on the optimum conditions.

Efficient syntheses of zoledronic acid as an active ingredient of a drug against osteoporosis

ABSTRACT The reaction of 1H-imidazol-1-ylacetic acid and two equivalents of phosphorus trichloride/phosphorous acid at 75 °C in sulfolane, or in the presence of catalytic amounts of [bmim][BF4] afforded zoledronic acid in yields up to 75%. The joint use of the ionic liquid additive and sulfolane as the solvent was synergetic affording highly valuable zoledronic acid in a record yield of 93%. GRAPHICAL ABSTRACT

The synthesis of dronic acid derivatives in sulfolane or in the presence of ionic liquids as additives

GRAPHICAL ABSTRACT ABSTRACT The synthesis of dronic acid derivatives was investigated in different solvents (in sulfolane or in the presence of ionic liquids as additives). In these variations, phosphorous acid also has a role as an active reactant.