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Optimized Synthesis of Etidronate

[ Vol. 10 , Issue. 8 ]


Rita Kovacs, David Illes Nagy, Alajos Grün, Gyorgy Tibor Balogh, Sandor Garadnay, Istvan Greiner and Gyorgy Keglevich   Pages 733 - 737 ( 5 )


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.


Hydroxy-methylenebisphosphonic acid, Etidronate, Optimization, Intermediate.


Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary.

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