3-Pyridineacetic acid → Risedronate

Participants

Reaction Conditions

Reaction Steps

The suspension of (3-pyridyl)ethanoic acid (10.0 g) and phosphorous acid (17.9 g) in diphenyl ether (50 ml) was heated up to 70° C. for 1 hour. Phosphorous trichloride (19.1 ml) was slowly added to reaction mass at 70° C. temperature and maintained reaction temperature for another 6 hours. Reaction mass was cooled to 25° C. followed by addition of water (150 ml) and toluene (30 ml). The reaction mixture was again heated to 70° C. and charged charcoal in hazy biphasic solution, stirred, filtered through Hyflo bed, washed the bed with hot water (30 ml). Layers was separated from filtrate, aqueous layer was washed with toluene (20 ml) and combined organic layer was then back extracted with water (20 ml) and mixed with main aqueous layer. The water (140 ml) was distilled out from combined aqueous layer at atmospheric pressure in 2 hours and then refluxed the concentrated mass for 13 hours. Reaction mass was cooled to 25° C. followed by addition of methanol (150 ml) in 1 hours, stirred and again cooled to 0° C., filtered, washed with chilled 1:2 mixture (30 ml) of water and methanol and dried at 60° C. to get Risedronic acid.

Provenance & Evidence