Abstract
Background: The synthesis of high value risedronic acid is not fully resolved, as, for the time being, the best method based on the preparation from 3-pyridylcarboxylic acid by reaction with phosphorus trichloride in methanesulfonic acid gives risedronic acid in a good yield, but in an unpure form.
Methods: Alternative protocols realizing the synthesis in sulfolane as the solvent and/or in the presence of suitable IL additive were developed to obtain the target dronic acid in a pure form.
Results & Conclusion: Using phosphorus trichloride and phosphorous acid in two equivalents quantities together with 0.6 equivalents of [bmim][BF4] without any solvent, the method afforded the target dronic acid in a yield of 66% in a pure form.
Keywords: Risedronic acid, 3-pyridylacetic acid, P-reagents, sulfolane, ionic liquid additive, optimization.
Graphical Abstract
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