反应详情

Trichloromethyl chloroformate (0.39 g, 2.0 mmol) was added to a solution of 3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.59 g, 2.0 mmol) in chloroform (10 ml) at 0° C., and while the mixture was allowed to have room temperature gradually, 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, the reaction mixture was refluxed under heating for 5 hours. After completion of the reaction, the reaction mixture was poured into ice water and extracted with chloroform (20 ml×3). An organic layer was washed with water, dried over anhydrous magnesium sulfate and filtered to remove a desiccant, and the solvent was distilled off from the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/10→1/5), 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): δ 1.50-1.65 (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, JHF=1.9 and 9.3 Hz, 1H), 7.56 (s, 1H).

1. customto have room temperature
2. temperaturethe reaction mixture was refluxed
3. temperatureunder heating for 5 hours
4. customAfter completion of the reaction
5. extractionextracted with chloroform (20 ml×3)
6. washAn organic layer was washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. customto remove a desiccant, and the solvent
10. distillationwas distilled off from the filtrate under reduced pressure
11. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/10→1/5)