反应详情

温度

70 °C

2,3-Difluorophenol (46) (13.8 g) and tripotassium phosphate (K3PO4; 73.4 g) were added to DMF (200 ml) under a nitrogen atmosphere, and the mixture was stirred at 70° C. The compound (15) (20.0 g) was added thereto and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C., solids were separated by filtration, and then toluene (100 ml) and water (100 ml) were added to and mixed with the filtrate. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and extraction into an organic phase was carried out. The organic phase obtained was fractionated, washed with brine, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue obtained was purified with a fractional operation by means of column chromatography using toluene as the eluent and silica gel as the stationary phase powder. The product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and ethyl acetate (Solmix A-11:ethyl acetate=2:1 by volume) and dried, giving 19.8 g of 2,3-difluoro-4-ethoxy-[trans-4-(2,3-difluorophenoxymethyl)cyclohexyl]benzene (47). The yield based on the compound (15) was 74.8%.

1. customAfter the reaction mixture obtained
2. temperaturehad been cooled to 30° C.
3. customsolids were separated by filtration
4. additiontoluene (100 ml) and water (100 ml) were added to and
5. additionmixed with the filtrate
6. customhad separated into two phases of organic and
7. extractionaqueous phases, and extraction into an organic phase
8. customThe organic phase obtained
9. washwashed with brine
10. dry with materialdried over anhydrous magnesium sulfate
11. distillationThen, the solvent was distilled off under reduced pressure
12. customthe residue obtained
13. customwas purified with a fractional operation by means of column chromatography
14. customThe product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and ethyl acetate (Solmix A-11:ethyl acetate=2:1 by volume)
15. customdried