Submit Manuscript  

Article Details


Efficient Synthesis of Ibandronate in the Presence of an Ionic Liquid

[ Vol. 15 , Issue. 7 ]

Author(s):

David Illes Nagy, Alajos Grun, Oliver Pavela, Sandor Garadnay, Istvan Greiner and Gyorgy Keglevich*   Pages 713 - 720 ( 8 )

Abstract:


Background: Ibandronate is a prominent representative of α-hydroxymethylenebisphosphonic acid (dronic acid) derivatives applied in the treatment of bone diseases.

Methods: Ibandronate was synthesized from N-methyl-N-pentyl-β-alanine using phosphorus trichloride and phosphorous acid in different ratios, applying sulfolane as the solvent (1.), or under solvent-free conditions (2.), or in ionic liquids as additives (3.).

Results: In the first two cases (1. and 2.), using phosphorus trichloride and phosphorous acid in molar ratios of 2:4 and 3:4, pure ibandronate was obtained in yields of 72-83%. In the presence of 10% of [bmim][BF4] as an additive (3.), a better yield of 82/90% was obtained applying ratios of 2:2 and 3:2 of the P-reagents assuming less of the phosphorous acid.

Conclusion: The new methods developed mean record outcomes in respect of the valuable drug, ibandronate.

Keywords:

Ibandronate, N-methyl-N-pentyl-β-alanine, P-reagents, sulfolane, ionic liquid additive, osteoporosis.

Affiliation:

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest 1521, Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest 1521, Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest 1521, Gedeon Richter Plc., Budapest 1475, Gedeon Richter Plc., Budapest 1475, Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest 1521

Graphical Abstract:



Read Full-Text article