반응 #442598

반응 방정식

sodium hydride

3-quinuclidinone

borane THF

Sodium hydride

triethyl 2-fluoro-2-phosphonoacetate

→

title compound

수율 70.5%

Borane-[ethyl fluoro-(3-quinuclidinylidene)acetate]

수율 70.5%

용매

THF

acetic acid

water

THF

Water

반응 조건

후처리

1. 1
   온도cooling
2. 2
   workup.STIRRINGthe mixture was stirred at room temperature for 5 days
3. 3
   농축the mixture was concentrated under a reduced pressure
4. 4
   workup.ADDITIONWater (2.5 l) was added to the residue
5. 5
   추출the reaction product was extracted with chloroform (1.5 l×2)
6. 6
   세척The extract was washed with saturated sodium chloride aqueous solution
7. 7
   건조dried over anhydrous magnesium sulfate
8. 8
   농축concentrated under a reduced pressure
9. 9
   workup.ADDITIONTHF (1.0 l) was added to the resulting yellow oily material
10. 10
    온도cooling
11. 11
    workup.WAITspending 2.5 hours
12. 12
    workup.STIRRINGAfter additional 0.5 hour of stirring
13. 13
    농축the mixture was concentrated under a reduced pressure
14. 14
    workup.ADDITIONEthyl acetate was added to the resulting residue
15. 15
    세척the mixture was washed with water and saturated sodium chloride aqueous solution in that order
16. 16
    건조dried over anhydrous magnesium sulfate
17. 17
    농축concentrated under a reduced pressure
18. 18
    세척The resulting residue was washed with hexane (400 ml)
19. 19
    기타dried under a reduced pressure
20. 20
    workup.ADDITIONEthanol (2.8 l) was added to the resulting brown solid (402 g)
21. 21
    workup.STIRRINGthe mixture was stirred for 7 hours
22. 22
    농축the mixture was concentrated under a reduced pressure
23. 23
    workup.ADDITIONEthyl acetate was added to the residue
24. 24
    세척the mixture was washed with water and saturated sodium chloride aqueous solution in that order
25. 25
    건조dried over anhydrous magnesium sulfate
26. 26
    농축concentrated under a reduced pressure
27. 27
    workup.ADDITIONEthanol (1.2 l) was added to the resulting brown solid
28. 28
    workup.STIRRINGthe mixture was stirred for 20 minutes
29. 29
    기타The insoluble matter was removed by filtration
30. 30
    농축the resulting filtrate was concentrated under a reduced pressure

실험 절차

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.

출처