反应详情

温度

-50 °C

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.

1. temperaturewhile being maintained at the same temperature, and they
2. temperaturewhile being maintained at the same temperature
3. stirringstirred for 2 hours
4. stirringstirred for 2 hours
5. customto terminate
6. customthe reaction
7. distillationthe solvent was distilled off under a reduced pressure
8. extractionthe residue was extracted with 500 ml of toluene
9. washthe organic layer was washed with 100 ml of water thrice
10. dry with materialdried over anhydrous magnesium sulfate
11. customAfter the anhydrous magnesium sulfate was removed by filtration, 2.83 g of p-toluenesulfonic acid monohydrate
12. additionwas added to the filtrate
13. temperatureheated
14. temperatureto reflux for 4 hours
15. washThe organic layer was washed with 200 ml of water thrice
16. dry with materialdried over anhydrous magnesium sulfate
17. distillationThe solvent was distilled off under a reduced pressure
18. additionthe residue was subjected to silica gel column chromatography (eluent: mixed solvent of heptane/toluene=7/3)