反应详情

To a solution of 2′-fluoroacetophenone (28.6 g) in ethyl acetate (400 mL), copper (II) bromide (92.6 g) was added, and the mixture was heated under reflux for 4 hr. The reaction mixture was cooled to room temperature and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure to give crude 1-bromo-1-(2-fluorophenyl)ethanone (yield 90.5 g) as an oil. Potassium carbonate (88 g) was added to ethyl cyanoacetate (168 g), and the mixture was stirred at 45° C. for 1 hr. A solution (360 mL) of crude 1-bromo-1-(2-fluorophenyl)ethanone (90.5 g) in acetone was added dropwise over 20 min. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hr. To the reaction mixture water (300 mL) and ethyl acetate (300 mL) were added, and the mixture was extracted with ethyl acetate. The extract was washed with 10% aqueous sodium dihydrogenphosphate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. An excess ethyl cyanoacetate contained in the obtained oil was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=20:1→4:1) to give the title compound as an oil (yield 64.0 g, about 100%).

1. temperaturethe mixture was heated
2. temperatureunder reflux for 4 hr
3. filtrationthe insoluble material was filtered off
4. concentrationThe filtrate was concentrated under reduced pressure
5. customto give crude 1-bromo-1-(2-fluorophenyl)ethanone (yield 90.5 g) as an oil
6. additionAfter completion of the dropwise addition
7. stirringthe mixture was stirred at the same temperature for 1 hr
8. extractionthe mixture was extracted with ethyl acetate
9. washThe extract was washed with 10% aqueous sodium dihydrogenphosphate solution and saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customwas evaporated under reduced pressure
13. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=20:1→4:1)