反应详情

Trichloromethyl chloroformate (0.39 g, 2.0 mmol) was added to a chloroform (10 mL) solution of 3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.59 g, 2.0 mmol) at 0° C., and while the mixture was allowed to gradually warm up to a room temperature, it was further stirred at room temperature for 3 hours. Tetrahydrofurfurylamine (0.61 g, 6.0 mmol) and triethylamine (0.4 g, 4.0 mmol) were added to the reaction mixture, and the mixture was refluxed under heating for 5 hours. After completion of the reaction, the reaction mixture was poured into ice and extracted with chloroform (20 mL×3 times). The organic layer was washed with water and dried over anhydrous magnesium sulfate, the desiccant was removed by filtering, and the solvent was distilled off the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane= 1/10˜⅕) to give a colorless viscous substance of N-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide (0.25 g, yield: 29.6%). 1H-NMR (CDCl3, TMS, ppm): δ1.50-1.65 (m, 1H), 1.75˜2.05 (m, 3H), 2.58 (s, 3H), 3.32 (dt, J=6.3 and 13.9 Hz, 1H), 3.48 (ddd, J=3.7, 5.7 and 13.9 Hz, 1H), 3.74 (dq, J=7.0 and 8.6 Hz, 2H), 4.03 (dq, J=3.7 and 7.0 Hz, 1H), 5.79 (s, 1H), 6.85˜7.10 (m, 1H), 7.39 (dd, J=1.9 and JHF=9.3 Hz, 1H), 7.56 (s, 1H).

1. temperaturethe mixture was refluxed
2. temperatureunder heating for 5 hours
3. customAfter completion of the reaction
4. additionthe reaction mixture was poured into ice
5. extractionextracted with chloroform (20 mL×3 times)
6. washThe organic layer was washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. customthe desiccant was removed
9. filtrationby filtering
10. distillationthe solvent was distilled off the filtrate under reduced pressure
11. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane= 1/10˜⅕)