Gamma-Aminobutyric Acid → Alendronic acid monohydrate

Participants

Reaction Conditions

Reaction Steps

A 500 ml cylindrical reactor equipped with a mechanical stirrer, a thermometer, a reflux condenser and a dropping funnel, was loaded with GABA (4.12 g, 0.04 mole), phosphorous acid (9.84 g, 0.12 mole) and toluene (50 ml). The suspension was heated to 90° C. Hyfllo Super-Cel diatomaceous silica (17.50 g, 50% w/w of all the reagents) was added in portions after the mixture of 3-pyridyl acetic acid HCL and H3PO3 was melted to obtain an heterogeneous suspension. Phosphorous oxychloride (11.2 ml, 0.12 mole) was then added dropwise during 12 minutes. The reaction mixture was then heated to 95° C. for 3 hours. Water (75 ml) was added after cooling the reaction mixture to 65° C. The mixture was stirred vigorously for 30 minutes and then the Hyfllo was removed by filtration. The toluene and the aqueous phases were separated and the aqueous phase was heated at 95° C. for 16 hours. The aqueous phase was cooled to 25° C. and absolute ethanol (75 ml) was added to precipitate the final product. The suspension was cooled to 5° C. for 1 hour. The white product was filtered, washed with absolute ethanol (2×20 ml) and dried in a vacuum oven at 50° C. for 24 hours to obtain 5.60 g (56%) of alendronic acid monohydrate.

Provenance & Evidence