反应详情

温度

64 °C

A 250 mL three-necked round-bottomed flask was charged with {(5-chloro-benzo[b]thiophen-3-yl)-[2-(3,4-difluoro-phenyl)-vinylcarbamoyl]-methyl}-methyl-phosphinic acid (20.0 g, 42.2 mol) and methanol (150 mL), under nitrogen. To the resulting slurry was then added 45% by wt. of choline hydroxide in methanol (12.8 mL, 45.3 mol), in one portion. Shortly after the addition, a homogeneous clear solution was obtained. The solution was aged at room temperature for about 1 hour, then clarified by filtration through a medium sintered glass filter. The resulting filtered solution was concentrated by distillation (at a temperature of about 63-65° C.) to a residual volume of about 55-60 mL. While at the elevated temperature, EtOAc (140-150 mL) was added by an addition funnel over a period of about 40 minutes, while maintaining a temperature of about 63-65° C. The resulting clear solution was seeded, then cooled slowly under moderate agitation to ambient temperature. The resulting slurry was then aged overnight, cooled to about 5-10° C. and aged at this temperature for about 2 hours. The resulting solid was collected by filtration, rinsed with cold EtOAc (40 mL, 2C) and dried in a vacuum oven at 50° C., overnight to yield the title compound as a white crystalline solid.

1. additionShortly after the addition
2. customa homogeneous clear solution was obtained
3. filtrationclarified by filtration through a medium sintered glass
4. filtrationfilter
5. filtrationThe resulting filtered solution
6. concentrationwas concentrated by distillation (at a temperature of about 63-65° C.) to a residual volume of about 55-60 mL
7. additionWhile at the elevated temperature, EtOAc (140-150 mL) was added by an addition funnel over a period of about 40 minutes
8. temperaturecooled slowly under moderate agitation to ambient temperature
9. waitThe resulting slurry was then aged overnight
10. temperaturecooled to about 5-10° C.
11. waitaged at this temperature for about 2 hours
12. filtrationThe resulting solid was collected by filtration
13. washrinsed with cold EtOAc (40 mL, 2C)
14. customdried in a vacuum oven at 50° C., overnight