反应详情

温度

80 °C

To a stirring solution of 6-bromo-3-(difluoromethoxy)-2-methoxyphenol (200 mg, 0.74 mmol) in acetonitrile (10 mL) was added potassium carbonate (307 mg, 2.23 mmol) and ethyl bromide (0.6 mL, 2.23 mmol) and the resultant reaction mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure to afford 200 mg of crude product, 1-Bromo-4-difluoromethoxy-2-ethoxy-3-methoxy-benzene, as a solid. A stirring solution of 1-bromo-4-(difluoromethoxy)-2-ethoxy-3-methoxybenzene (200 mg, 0.673 mmol) in N,N-dimethylformamide (5 mL) was purged with argon for 1 h, to this cesium carbonate (656 mg, 2.019 mmol), tetrakis(triphenylphosphine) palladium(0) (38 mg, 0.033 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (209 mg, 0.807 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded the title compound as a solid (30 mg, 13%).

1. customthe resultant reaction mixture
2. temperatureThe reaction mixture was cooled to RT
3. filtrationfiltered through celite
4. concentrationthe filtrate was concentrated under reduced pressure
5. customto afford 200 mg of crude product, 1-Bromo-4-difluoromethoxy-2-ethoxy-3-methoxy-benzene
6. additionwere added
7. customthe resultant reaction mixture
8. temperaturewas heated to 80-90° C. for 3 h
9. temperatureThe reaction mixture was cooled to RT
10. filtrationfiltered
11. additionthe filtrate was diluted with water
12. extractionextracted with ethyl acetate (3×)
13. washThe combined ethyl acetate layer was washed with brine
14. dry with materialdried over anhydrous sodium sulphate
15. concentrationconcentrated under reduced pressure
16. customPurification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether)