反应 #1076763

反应方程式

water

sec-butyl lithium

1-ethoxy-2,3-difluorobenzene

4-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)butanal

→

1-ethoxy-2,3-difluoro-4-(4-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)-1-butenyl)benzene

收率 74.0%

溶剂

THF

THF

反应条件

后处理

1. 1
   温度while being maintained at the same temperature, and they
2. 2
   温度while being maintained at the same temperature
3. 3
   workup.STIRRINGstirred for 2 hours
4. 4
   workup.STIRRINGstirred for 2 hours
5. 5
   其他to terminate
6. 6
   其他the reaction
7. 7
   workup.DISTILLATIONthe solvent was distilled off under a reduced pressure
8. 8
   萃取the residue was extracted with 500 ml of toluene
9. 9
   洗涤the organic layer was washed with 100 ml of water thrice
10. 10
    干燥dried over anhydrous magnesium sulfate
11. 11
    其他After the anhydrous magnesium sulfate was removed by filtration, 2.83 g of p-toluenesulfonic acid monohydrate
12. 12
    workup.ADDITIONwas added to the filtrate
13. 13
    温度heated
14. 14
    温度to reflux for 4 hours
15. 15
    洗涤The organic layer was washed with 200 ml of water thrice
16. 16
    干燥dried over anhydrous magnesium sulfate
17. 17
    workup.DISTILLATIONThe solvent was distilled off under a reduced pressure
18. 18
    workup.ADDITIONthe residue was subjected to silica gel column chromatography (eluent: mixed solvent of heptane/toluene=7/3)

实验过程

Under nitrogen gas stream, a solution of 30.7 g (194 mmol) of 1-ethoxy-2,3-difluorobenzene in 300 ml of THF was cooled down to −70° C., 194 ml of sec-butyl lithium (1.0M cyclohexane solution) was added by drops thereto while being maintained at the same temperature, and they were stirred at the same temperature for 2 hours. To this reaction mixture was added by drops a solution of 45.1 g (162 mmol) of the crude 4-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)butanal obtained by the reaction in the fifth step in 450 ml of THF while being maintained at the same temperature, and stirred for 2 hours. Subsequently, they were raised up to −50° C. and stirred for 2 hours. The reaction mixture was added to 200 ml of water to terminate the reaction, the solvent was distilled off under a reduced pressure, the residue was extracted with 500 ml of toluene, and the organic layer was washed with 100 ml of water thrice, and then dried over anhydrous magnesium sulfate. After the anhydrous magnesium sulfate was removed by filtration, 2.83 g of p-toluenesulfonic acid monohydrate was added to the filtrate, and heated to reflux for 4 hours. The organic layer was washed with 200 ml of water thrice and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure and the residue was subjected to silica gel column chromatography (eluent: mixed solvent of heptane/toluene=7/3) to obtain 50.2 g of a crude 1-ethoxy-2,3-difluoro-4-(4-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)-1-butenyl)benzene.

来源