Phosphorus trichloride → Risedronate

Participants

Reaction Conditions

Reaction Steps

A suspension of 3-pyridylacetic acid hydrochloride (50 g, 0.288 mol) and phosphorous acid (35.4 g, 0.432 mol) in sulfolane (180 ml) is heated to 75° C. for 30 min. The mixture is cooled to 35-40° C. and then gradually introduced phosphorous trichloride (85.6 ml, 0.98 mol) while maintaining the temperature between 35-45° C. The mixture is heated to 63-67° C. for 3 hours whereby a thick white mass results. It is then cooled to 0-5° C. and quenched by slow addition of water (500 ml) at 0-5° C. over a period of 1 hour. The resulting clear solution is charcoalized and heated at 100° C. for 3 hrs, cooled to ambient temperature and then cooled 0-5° C. After stirring for 2 hrs at 0-5° C. the crystallized product is filtered, washed sequentially with chilled water (100 ml), rectified spirit (75 ml) and dried in air oven at 55-60° C. until loss on drying is less than 0.5% w/w. Yield 60.4 g, (70.47%), appearance: white crystalline solid, purity >99.0%.

Provenance & Evidence