Phosphoric Acid → Risedronate

온도

90 °C

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.

1. temperatureThe reaction mixture was then heated to 95° C. for 20.5 hours
2. temperatureafter cooling the reaction mixture to 80° C
3. dissolutiondissolved completely
4. customThe toluene and the aqueous phases were separated
5. temperaturethe aqueous phase was heated at 95° C. for 5.5 hours
6. temperatureThe aqueous phase was cooled to 25° C.
7. additionabsolute ethanol (200 ml) was added
8. customto precipitate the final product
9. temperatureThe suspension was cooled to 5° C. for 1 hour
10. filtrationThe white product was filtered
11. washwashed with absolute ethanol (2×80 ml)
12. customdried at 65° C. for 5 hours

ORD 기록

ord-bd6b69083f0e4c119261277edbb47e6a

출처 데이터셋

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07038083B2