A Study on the Synthesis of Risedronic Acid: The Role of an Ionic Liquid Additive

Author(s): Dávid Illés Nagy, Alajos Grün, Júlia Sinkovicz, Sándor Garadnay, István Greiner, György Keglevich*

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 3 , 2019

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Graphical 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.

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Article Details

Year: 2019
Page: [238 - 244]
Pages: 7
DOI: 10.2174/1570180815666180626122630

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