3-Pyridineacetic acid → Risedronate

Temperature

70 °C

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.

1. temperaturemaintained
2. customreaction temperature for another 6 hours
3. customReaction mass
4. temperaturewas cooled to 25° C.
5. temperatureThe reaction mixture was again heated to 70° C.
6. filtrationfiltered through Hyflo bed
7. washwashed the bed with hot water (30 ml)
8. customLayers was separated from filtrate, aqueous layer
9. washwas washed with toluene (20 ml)
10. extractionwas then back extracted with water (20 ml)
11. additionmixed with main aqueous layer
12. distillationThe water (140 ml) was distilled out
13. customin 2 hours
14. temperaturerefluxed the concentrated mass for 13 hours
15. customReaction mass
16. temperaturewas cooled to 25° C.
17. stirringstirred
18. temperatureagain cooled to 0° C.
19. filtrationfiltered
20. washwashed
21. temperaturewith chilled 1:2 mixture (30 ml) of water and methanol
22. customdried at 60° C.

ORD record

ord-6ba843df276546f29b38e1bc64635033

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07439385B2