反応 #2175426

反応方程式

4-(2,3-difluorophenyl)cyclohexanone

sec-Butyllithium

ammonium chloride

3-Butoxy-1,2-difluorobenzene

→

1-butoxy-4-(4-(2,3-difluorophenyl)cyclohex-1-enyl)-2,3-difluorobenzene

収率 20.0%

溶媒

THF

n-hexane

cyclohexane

ethyl acetate

THF

反応条件

後処理

1. 1
   workup.ADDITION114 ml) was added dropwide
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   workup.WAITin the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture
4. 4
   その他to come to 25° C
5. 5
   workup.ADDITIONThe reaction mixture was poured into a vessel
6. 6
   workup.ADDITIONmixed with them
7. 7
   その他had separated into organic and aqueous phases
8. 8
   抽出the extraction
9. 9
   洗浄The combined organic phase was washed successively with water
10. 10
    乾燥a saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate
11. 11
    workup.DISTILLATIONThen, the solvent was distilled off under the reduced pressure
12. 12
    workup.ADDITIONp-Toluenesulfonic acid (4.1 g) and toluene (300 ml) were added to the residue
13. 13
    温度the mixture was heated
14. 14
    温度to reflux for 2 hours
15. 15
    workup.DISTILLATIONwhile distilled water
16. 16
    その他was removed
17. 17
    workup.ADDITIONwater (500 ml) and toluene (500 ml) were added to the mixture
18. 18
    workup.ADDITIONmixed with it
19. 19
    その他had separated into two phases of organic and aqueous phases
20. 20
    抽出the extraction
21. 21
    洗浄The combined organic phase was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and water
22. 22
    乾燥dried over anhydrous magnesium sulfate
23. 23
    その他The solution was purified by column chromatography
24. 24
    その他a mixed solvent of toluene and heptane (1/1 by volume) as an eluent, and then by recrystallization from Solmix A-11

実験手順

3-Butoxy-1,2-difluorobenzene (s-18) (17.7 g) and THF (500 ml) were put in a reaction vessel under an atmosphere of nitrogen and cooled to −74° C. sec-Butyllithium (a 1.00 M solution in n-hexane and cyclohexane; 114 ml) was added dropwide thereto in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. Then, 4-(2,3-difluorophenyl)cyclohexanone (s-19) (20.0 g) dissolved in THF (100 ml) was added dropwise thereto in the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture was allowed to come to 25° C. The reaction mixture was poured into a vessel containing an aqueous solution of ammonium chloride (3%; 200 ml) and ethyl acetate (200 ml), and mixed with them. The mixture was then allowed to stand until it had separated into organic and aqueous phases, and the extraction was carried out. The combined organic phase was washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under the reduced pressure. p-Toluenesulfonic acid (4.1 g) and toluene (300 ml) were added to the residue and the mixture was heated to reflux for 2 hours, while distilled water was removed. After the reaction mixture had been cooled to 30° C., water (500 ml) and toluene (500 ml) were added to the mixture, and mixed with it. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and the extraction was carried out. The combined organic phase was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate. The solution was purified by column chromatography using silica gel as a stationary phase powder and a mixed solvent of toluene and heptane (1/1 by volume) as an eluent, and then by recrystallization from Solmix A-11 to give 1-butoxy-4-(4-(2,3-difluorophenyl)cyclohex-1-enyl)-2,3-difluorobenzene (s-20) (7.2 g). The yield based on the compound (s-18) was 20.0%.

出典