Phosphoric Acid → Risedronate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A 2L cylindrical reactor equipped with a mechanical stirrer, a thermometer, a reflux condenser and a dropping funnel, was charged with 3-pyridine acetic acid hydrochloride (27.7 g, 0.16 mole), phosphorous acid (39.4 g, 0.48 mole), ortho-phosphoric acid (47.2 g, 0.48 mole) and toluene (200 ml). The suspension was heated to 90° C. and phosphorous oxychloride (44.8 ml, 0.48 mole) was added dropwise during 20 minutes. The reaction mixture was then heated to 95° C. for 20.5 hours. Water (200 ml) was added after cooling the reaction mixture to 80° C. The mixture was stirred vigorously until the solidified product dissolved completely. The toluene and the aqueous phases were separated and the aqueous phase was heated at 95° C. for 5.5 hours. The aqueous phase was cooled to 25° C. and absolute ethanol (200 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 (2×80 ml) and dried at 65° C. for 5 hours to obtain 38.2 g (84%) of risedronic acid monohydrate.

Herkunft & Nachweise