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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

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 and György Keglevich*

Volume 16, Issue 3, 2019

Page: [238 - 244] Pages: 7

DOI: 10.2174/1570180815666180626122630

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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