反应 #1076767

反应方程式

3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propyl 2,3-difluorophenyl ether

2,3-difluoro-1-bromobenzene

water

sec-butyl lithium

→

3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propyl 2,3-difluoro-4-(2,3-difluorophenyl)phenyl ether

溶剂

THF

THF

反应条件

后处理

1. 1
   温度while being maintained at the same temperature
2. 2
   workup.STIRRINGstirred at the same temperature for 1 hour
3. 3
   温度the reaction temperature was gradually raised up to room temperature, and they
4. 4
   workup.STIRRINGwere stirred for 1 hour
5. 5
   温度heated
6. 6
   温度to reflux for 3 hours
7. 7
   其他to terminate
8. 8
   其他the reaction
9. 9
   workup.DISTILLATIONthe solvent was distilled off under a reduced pressure
10. 10
    萃取the residue was extracted with 3.0 l of toluene
11. 11
    洗涤The organic layer was washed with 1.0 l of water thrice
12. 12
    干燥dried over anhydrous magnesium sulfate
13. 13
    workup.DISTILLATIONThe solvent was distilled off under a reduced pressure

实验过程

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.

来源