反应详情

温度

5 °C

To a mixture of 73 g (3.0 mole, 3 eq) of magnesium turnings in 700 mL of THF was added 40 g (0.25 mole) of 1-chloro-3-fluoro-2-[(1,1-dimethylethoxy)-methyl]benzene followed by 1 mL of 1,2-dibromoethane. The reaction mixture was heated at reflux temperature and over the next four hours another 1 mL of 1,2-dibromoethane was added in two portions. At the end of that time period, gas chromatography indicated Grignard formation had commenced. The remaining 177 g of the chlorofluorobenzene added over one hour, and the mixture was heated at reflux temperature for an additional 12 hours. The resulting cloudy dark brown mixture was cooled to 5° C. with an ice-bath and was added via nitrogen pressure cannulation to a solution of 163 mL (1.2 mole) of diethyloxalate in 300 mL of THF. The temperature during addition was maintained between -60° and -50° C. via dry ice/acetone bath cooling, and the addition was complete in 45 minutes. After allowing the mixture to warm to 0° C., 100 mL of 2N HCl was added, followed by 200 mL of water and concentrated HCl to bring the pH to 2. The THF was removed in vacuo, EtOAc was added, and the mixture washed with water, brine, and concentrated in vacuo to give a dark liquid. Distillation using a 5-tray Oldershaw column gave 172 g of ethyl 3-fluoro-2-[(1,1-dimethylethoxy)methyl]-α-oxo-benzeneacetate as a light yellow oil (bp 113-117° C./0.35 mm Hg.).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux temperature
3. temperaturethe mixture was heated
4. temperatureat reflux temperature for an additional 12 hours
5. additionThe temperature during addition
6. temperaturewas maintained between -60° and -50° C. via dry ice/acetone bath
7. temperaturecooling
8. additionthe addition
9. temperatureto warm to 0° C.
10. customThe THF was removed in vacuo, EtOAc
11. additionwas added
12. washthe mixture washed with water, brine
13. concentrationconcentrated in vacuo
14. customto give a dark liquid
15. distillationDistillation