Beta-Alanine → Pamidronic Acid

Temperature

75 °C

A suspension of 3-aminopropionic acid (25 g, 0.280 mol) and phosphorous acid (34.5 g, 0.421 mol) in sulfolane (90 ml) is heated to 75° C. for 30 min. The mixture is cooled to 35-40° C. and then gradually introduced phosphorous trichloride (83 ml, 0.954 mol) while maintaining the temperature at 35-45° C. The mixture is heated to 63-67° C. for 3 hrs, whereby white solid results. It is then cooled to 0-5° C. and quenched by slow addition of water (250 ml) at 0-5° C. over a period of 1 hr. The resulting clear solution is charcoalized and is heated at 100° C. for 3 hrs, cooled to ambient temperature. Cooled the charcoalized solution and stirred for 4 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 water content is less than 0.5% w/w. Yield 41.4 g, (62.7%), appearance: white crystalline solid, purity >99.0%.

1. temperatureThe mixture is cooled to 35-40° C.
2. temperatureThe mixture is heated to 63-67° C. for 3 hrs
3. customwhereby white solid results
4. temperatureIt is then cooled to 0-5° C.
5. customquenched by slow addition of water (250 ml) at 0-5° C. over a period of 1 hr
6. temperatureis heated at 100° C. for 3 hrs
7. temperaturecooled to ambient temperature
8. temperatureCooled the charcoalized solution
9. filtrationThe crystallized product is filtered
10. washwashed sequentially with chilled water (100 ml), rectified spirit (75 ml)
11. dry with materialdried in air oven at 55-60° C. until water content

ORD record

ord-a229cc26271a41f0991ae32a43340594

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07411087B2