反应详情

温度

50 °C

Sodium hydride (60 wt. %, 83.6 g, 2.09 mol) was added to a mixture of triethyl 2-fluoro-2-phosphonoacetate (506 g, 2.09 mol) and THF (3.0 l) with ice-cooling, and the mixture was stirred for 2 hours. A THF (600 ml) solution of 3-quinuclidinone (238 g, 1.90 mol) was added and the mixture was stirred at room temperature for 5 days. Water (500 ml) was added to the reaction mixture and the mixture was concentrated under a reduced pressure. Water (2.5 l) was added to the residue, and then the reaction product was extracted with chloroform (1.5 l×2). The extract was washed with saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and then concentrated under a reduced pressure. THF (1.0 l) was added to the resulting yellow oily material, and then a borane-THF complex (1.0M THF solution, 2.1 l, 2.1 mol) was added dropwise with ice-cooling spending 2.5 hours. After additional 0.5 hour of stirring, water (400 ml) was added to the reaction mixture and the mixture was concentrated under a reduced pressure. Ethyl acetate was added to the resulting residue, the mixture was washed with water and saturated sodium chloride aqueous solution in that order, dried over anhydrous magnesium sulfate, and then concentrated under a reduced pressure. The resulting residue was washed with hexane (400 ml) and dried under a reduced pressure. Ethanol (2.8 l) was added to the resulting brown solid (402 g) and then, while heating at 50° C., sodium hydride (60 wt. %, 4.24 g, 106 mmol) was added, and the mixture was stirred for 7 hours. After spontaneous cooling, acetic acid (5.4 ml) was added to the reaction mixture, and the mixture was concentrated under a reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with water and saturated sodium chloride aqueous solution in that order, dried over anhydrous magnesium sulfate, and then concentrated under a reduced pressure. Ethanol (1.2 l) was added to the resulting brown solid, and the mixture was stirred for 20 minutes. The insoluble matter was removed by filtration and then the resulting filtrate was concentrated under a reduced pressure to give the title compound (304 g, E/Z mixture) as a brown oil.

1. temperaturecooling
2. stirringthe mixture was stirred at room temperature for 5 days
3. concentrationthe mixture was concentrated under a reduced pressure
4. additionWater (2.5 l) was added to the residue
5. extractionthe reaction product was extracted with chloroform (1.5 l×2)
6. washThe extract was washed with saturated sodium chloride aqueous solution
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under a reduced pressure
9. additionTHF (1.0 l) was added to the resulting yellow oily material
10. temperaturecooling
11. waitspending 2.5 hours
12. stirringAfter additional 0.5 hour of stirring
13. concentrationthe mixture was concentrated under a reduced pressure
14. additionEthyl acetate was added to the resulting residue
15. washthe mixture was washed with water and saturated sodium chloride aqueous solution in that order
16. dry with materialdried over anhydrous magnesium sulfate
17. concentrationconcentrated under a reduced pressure
18. washThe resulting residue was washed with hexane (400 ml)
19. customdried under a reduced pressure
20. additionEthanol (2.8 l) was added to the resulting brown solid (402 g)
21. stirringthe mixture was stirred for 7 hours
22. concentrationthe mixture was concentrated under a reduced pressure
23. additionEthyl acetate was added to the residue
24. washthe mixture was washed with water and saturated sodium chloride aqueous solution in that order
25. dry with materialdried over anhydrous magnesium sulfate
26. concentrationconcentrated under a reduced pressure
27. additionEthanol (1.2 l) was added to the resulting brown solid
28. stirringthe mixture was stirred for 20 minutes
29. customThe insoluble matter was removed by filtration
30. concentrationthe resulting filtrate was concentrated under a reduced pressure