反应详情

2,5-Difluoro-4-bromo-3-methylbenzoic acid (10.7 g, 42.4 mmol) was dissolved in toluene (160 mL). Thionyl chloride (5.00 mL, 63.9 mmol) and dimethylformamide (5.0 mL) were added, and the mixture was heated to reflux for two hours. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (300 mL). Ethyl 3-dimethylaminoacrylate (7.30 ml, 50.9 mmol) and triethylamine (7.60 mL, 54.5 mmol) were added, and the mixture was heated to reflux for three hours. The solvent was evaporated under reduced pressure, and dichloromethane and water were added to the residue to separate the layers. Then, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to flash column chromatography (hexane:ethyl acetate=2:1→1:1→1:2) to give the title compound (11.35 g) as a yellow oil.

1. temperaturethe mixture was heated
2. temperatureto reflux for two hours
3. customThe solvent was evaporated under reduced pressure
4. dissolutionthe residue was dissolved in tetrahydrofuran (300 mL)
5. temperaturethe mixture was heated
6. temperatureto reflux for three hours
7. customThe solvent was evaporated under reduced pressure, and dichloromethane and water
8. additionwere added to the residue
9. customto separate the layers
10. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
11. customthe solvent was evaporated under reduced pressure