反应详情

To a solution of 3-(2,2,2-trifluoroethoxy)toluene (7.34 g, 38.6 mmol) in carbon tetrachloride (100 ml) were added N-bromosuccinimide (7.56 g, 42.5 mmol) and 2,2′-azobis(isobutyronitrile) (633 mg, 3.86 mmol) and the mixture was heated under reflux overnight. The insoluble material was filtered using celite and the filtrate was concentrated to prepare a bromo form. To a solution of ethyl 3-oxo-3-(4-fluorophenyl)propionate (7.3 g, 34.7 mmol) in 1,2-dimethoxyethane (70 ml) was added sodium hydride (60% in oil, 1.39 g, 34.7 mmol) under ice-cooling and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of the bromo form synthesized above in 1,2-dimethoxyethane (20 ml) and the reaction solution was stirred at room temperature for 1 hr. The reaction solution was poured into water (200 ml) and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) and recrystallized from diisopropyl ether-hexane to give ethyl-3-(4-fluorophenyl)-3-oxo-2-((3-(2,2,2-trifluoroethoxy)phenyl)methyl)propionate (4.23 g, 31%).

1. temperaturethe mixture was heated
2. temperatureunder reflux overnight
3. filtrationThe insoluble material was filtered
4. concentrationthe filtrate was concentrated
5. customto prepare a bromo form
6. temperaturecooling
7. stirringthe reaction solution was stirred at room temperature for 1 hr
8. extractionextracted with ethyl acetate (200 ml×2)
9. washThe extract was washed with water and saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customevaporated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)
13. customrecrystallized from diisopropyl ether-hexane