反应详情

To a 250-mL round-bottomed flask, 3,4-difluoro-N-phenethylbenzamide (1.97 g, 7.54 mmol) and phosphorus pentoxide (3.25 g, 22.9 mmol) were suspended into 40 mL of toluene. Phosphorus oxychloride (3.51 mL, 37.7 mmol) was added and the mixture was refluxed for overnight. The mixture was cooled to RT. The supernatant contained only the starting material and was removed. Ice water (75 mL) was added to the residue in the flask and stirred to break up the solid into powder. EtOAc was added and the pH was adjusted to ˜12 with 3N aqueous potassium hydroxide. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow viscous oil. The crude product was purified by silica gel chromatography (20-70% EtOAc in hexanes) to afford the title compound as a clear oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.17-7.52 (m, 7H) 3.78-3.92 (m, 2H) 2.73-2.89 (m, 2H)

1. temperaturethe mixture was refluxed for overnight
2. customwas removed
3. additionIce water (75 mL) was added to the residue in the flask
4. additionEtOAc was added
5. customThe layers were separated
6. extractionthe aqueous phase was extracted with EtOAc
7. washThe combined organic phases were washed with water and saturated aqueous sodium chloride
8. dry with materialThe organic phase was dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto afford a yellow viscous oil
12. customThe crude product was purified by silica gel chromatography (20-70% EtOAc in hexanes)