反应详情

温度

-70 °C

Under nitrogen gas stream, 101 g (267 mmol) of the 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propyl 2,3-difluorophenyl ether obtained by the procedures described above was dissolved in 1.0 l of THF and cooled down to −70° C. To this solution was added by drops 320 ml of sec-butyl lithium (1.0M, cyclohexane solution) while being maintained at the same temperature, and stirred at the same temperature for 2 hours. To the reaction mixture was added by drops 640 ml of zinc chloride (0.5M, THF solution), and stirred at the same temperature for 1 hour, the reaction temperature was gradually raised up to room temperature, and they were stirred for 1 hour. To the reaction mixture was added 1.00 g of tetrakis(triphenylphosphine)palladium (0), and a solution of 61.8 g (15.9 mmol) of 2,3-difluoro-1-bromobenzene in 600 ml of THF was added by drops thereto, and heated to reflux for 3 hours. The reaction mixture was added to 1.0 l of water to terminate the reaction, the solvent was distilled off under a reduced pressure, and the residue was extracted with 3.0 l of toluene. The organic layer was washed with 1.0 l of water thrice and 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: toluene) to obtain 55.3 g of a crude 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propyl 2,3-difluoro-4-(2,3-difluorophenyl)phenyl ether.

1. temperaturewhile being maintained at the same temperature
2. stirringstirred at the same temperature for 1 hour
3. temperaturethe reaction temperature was gradually raised up to room temperature, and they
4. stirringwere stirred for 1 hour
5. temperatureheated
6. temperatureto reflux for 3 hours
7. customto terminate
8. customthe reaction
9. distillationthe solvent was distilled off under a reduced pressure
10. extractionthe residue was extracted with 3.0 l of toluene
11. washThe organic layer was washed with 1.0 l of water thrice
12. dry with materialdried over anhydrous magnesium sulfate
13. distillationThe solvent was distilled off under a reduced pressure