反应详情

温度

22.5 °C

A solution of potassium phosphate tribasic (160 g, 0.762 moles) in demineralised water (500 ml) was added over 15 minutes to a stirred slurry of sodium 1 -hydroxy-3-(2-methyl-1,1′-biphenyl-4-yl)-1-propanesulfonate (125 g, 0.381 moles) in toluene (1500 ml) and demineralised water (1000 ml). The mixture was stirred at 20-25° C. for 16 hours. The organic phase was separated and the aqueous phase was extracted with toluene (100 ml). The combined organic extracts were washed with demineralised water (1000 ml), and the solution was azeotropically dried by distillation of toluene at 40° C. under reduced pressure. The volume of solution was reduced to 250 ml, and allowed to cool to 20-25° C. Meanwhile, 3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester (112 g, 0.360 moles) was added portionwise over 10 minutes to a solution of sodium tert-butoxide (114 g, 1.175 moles) in toluene (1120 ml) at −10° C. under nitrogen. The mixture was stirred for 30 minutes at −10° C. The toluene solution prepared previously was added over 45 minutes between −10° C. and 0° C. The mixture was stirred at −10° C. for 1 hour and aqueous citric acid solution (10% w/v, 1000 ml) was added. The biphasic mixture was stirred at 20-25° C. for 16 hours. The organic phase was separated and washed with demineralised water (1000 ml) . The organic phase was azeotropically dried by distillation at 40° C. under reduced pressure at a constant volume of 1330 ml. The solution was maintained at 40-45° C., and a solution of adamantanamine (53 g, 0.350 moles) in toluene (665 ml) was added in one portion. The mixture was cooled to 20-25° C., and was stirred for 16 hours. The precipitate was collected by filtration, washed with toluene (150 ml) and dried in vacuo at 50° C. to leave the title compound as a colourless solid (153 g, 76% yield).

1. customThe organic phase was separated
2. extractionthe aqueous phase was extracted with toluene (100 ml)
3. washThe combined organic extracts were washed with demineralised water (1000 ml)
4. dry with materialthe solution was azeotropically dried by distillation of toluene at 40° C. under reduced pressure
5. temperatureto cool to 20-25° C
6. stirringThe mixture was stirred for 30 minutes at −10° C
7. additionwas added over 45 minutes between −10° C. and 0° C
8. stirringThe mixture was stirred at −10° C. for 1 hour
9. stirringThe biphasic mixture was stirred at 20-25° C. for 16 hours
10. customThe organic phase was separated
11. washwashed with demineralised water (1000 ml)
12. customThe organic phase was azeotropically dried by distillation at 40° C. under reduced pressure at a constant volume of 1330 ml
13. temperatureThe solution was maintained at 40-45° C.
14. temperatureThe mixture was cooled to 20-25° C.
15. stirringwas stirred for 16 hours
16. filtrationThe precipitate was collected by filtration
17. washwashed with toluene (150 ml)
18. customdried in vacuo at 50° C.