Hydrochloric Acid → HCID 86614657, compound

Temperature

50 °C

A mixture of butyl(2E)-3-{3-[7-chloro-3-(2-{[4-fluoro-2-(trifluoromethyl)phenyl]amino}-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl}acrylate (3.0 g), ethanol (9 ml) and 2N NaOH (9 ml) was stirred at 50° C. for 1.5 hours. After completion of the reaction, acetone (27 ml) was added to the reaction mixture at 50° C., and 6N HCl (3.5 ml) was added dropwise thereto to adjust pH to 0.6. The mixture was stirred at 50° C. for 30 minutes and then at 25° C. for 1 hour, and crystals were collected by filtration, and washed with acetone/water (2/1, 6 ml). To a mixture of the resulting crystals (2.79 g), acetone (2 ml) and water (6 ml) was added dropwise 5% aqueous ammonia (2.1 ml) with stirring at room temperature to adjust pH to 9.2 and dissolve the mixture. Toluene (4.5 ml) was added to the resulting solution and the mixture was stirred for 5 minutes and allowed to stand for 5 minutes to separate an aqueous layer. Acetone (12 ml) and activated charcoal (0.15 g) were added to the obtained aqueous layer and the mixture was stirred at room temperature for 15 minutes. The activated charcoal was removed by filtration, and washed with acetone (6 ml). The filtrate and washings were combined and warmed to 50° C., and 6N HCl (1.25 ml) was added dropwise thereto with keeping the temperature almost the same and stirring to adjust pH to 0.5 and precipitate crystals. The mixture was stirred at 50° C. for 30 minutes and then at about 25° C. for 1 hour, and the crystals were collected by filtration and washed with acetone/water (2/1, 6 ml) to obtain the title compound (2.54 g, yield 84.8%). This product contained 0.9 mol of acetone.

1. additionwas added to the reaction mixture at 50° C.
2. stirringThe mixture was stirred at 50° C. for 30 minutes
3. waitat 25° C. for 1 hour
4. filtrationcrystals were collected by filtration
5. washwashed with acetone/water (2/1, 6 ml)
6. additionTo a mixture of the resulting crystals (2.79 g), acetone (2 ml) and water (6 ml)
7. additionwas added dropwise 5% aqueous ammonia (2.1 ml)
8. stirringwith stirring at room temperature
9. dissolutiondissolve the mixture
10. additionToluene (4.5 ml) was added to the resulting solution
11. stirringthe mixture was stirred for 5 minutes
12. waitto stand for 5 minutes
13. customto separate an aqueous layer
14. additionAcetone (12 ml) and activated charcoal (0.15 g) were added to the obtained aqueous layer
15. stirringthe mixture was stirred at room temperature for 15 minutes
16. customThe activated charcoal was removed by filtration
17. washwashed with acetone (6 ml)
18. temperaturewarmed to 50° C.
19. addition6N HCl (1.25 ml) was added dropwise
20. stirringstirring
21. stirringThe mixture was stirred at 50° C. for 30 minutes
22. waitat about 25° C. for 1 hour
23. filtrationthe crystals were collected by filtration
24. washwashed with acetone/water (2/1, 6 ml)

ORD record

ord-12b7983c10db4dceb33956777326f5b5

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07541478B2