Phosphoric Acid → Risedronate

温度

90 °C

A 500 ml cylindrical reactor equipped with a mechanical stirrer, a thermometer, a reflux condenser and a dropping funnel, was charged with 3-pyridine acetic acid hydrochloride (6.94 g, 0.04 mole), phosphorous acid (9.84 g, 0.12 mole), ortho-phosphoric acid (11.80 g, 0.12 mole) and toluene (50 ml). The suspension was heated to 90° C. and phosphorous oxychloride (11.2 ml, 0.12 mole) was added dropwise during 20 minutes. The reaction mixture was then heated to 95° C. for 20.5 hours. Water (50 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 (50 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 at 65° C. for 5 hours to obtain 7.70 g (68%) of risedronic acid monohydrate.

1. customA 500 ml cylindrical reactor equipped with a mechanical stirrer
2. temperatureThe reaction mixture was then heated to 95° C. for 20.5 hours
3. temperatureafter cooling the reaction mixture to 80° C
4. dissolutiondissolved completely
5. customThe toluene and the aqueous phases were separated
6. temperaturethe aqueous phase was heated at 95° C. for 5.5 hours
7. temperatureThe aqueous phase was cooled to 25° C.
8. additionabsolute ethanol (50 ml) was added
9. customto precipitate the final product
10. temperatureThe suspension was cooled to 5° C. for 1 hour
11. filtrationThe white product was filtered
12. washwashed with absolute ethanol (2×20 ml)
13. customdried at 65° C. for 5 hours

ORDレコード

ord-90cb7c4ff7244ae089de09e3826e2728

出典データセット

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07038083B2