反应详情

Trichloromethyl chloroformate (0.58 g, 3.0 mmol) was added to a solution of 3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole (0.55 g, 2.0 mmol) in ethyl acetate (10 ml) at 0° C., and the mixture was further stirred at an ambient temperature for 30 minutes. Then, the mixture was refluxed under heating for 1 hour. The solvent was distilled off from the reaction mixture and then the reaction mixture was cooled to 0° C. and dissolved in toluene (10 ml). Triethylamine (0.61 g, 6.0 mmol) and tetrahydrofurfurylamine (1.01 g, 10.0 mmol) were added, and while the mixture was allowed to have room temperature gradually, it was stirred for 1 hour. Then, the mixture was refluxed under heating for 2 hours. After completion of the reaction, the reaction mixture was poured into 1N hydrochloric acid (10 ml), and the mixture was extracted with ethyl acetate (10 ml×2). An organic layer was washed with water (10 ml×3), 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), to give a colorless viscous substance of N-tetrahydrofurfuryl-3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide (0.40 g, yield: 48.9%). 1H-NMR (CDCl3, TMS, ppm): δ 1.55-1.66 (m, 1H), 1.84-2.02 (m, 3H), 2.59 (d, J=0.8 Hz, 3H), 3.26-3.37 (m, 1H), 3.54 (ddd, J=3.7, 6.2 and 13.8 Hz, 1H), 3.71-3.90 (m, 2H), 4.00-4.16 (m, 1H), 5.74 (q, J=0.8 Hz, 1H), 7.18 (br s, 1H), 7.25 (d, J=8.7 Hz, 1H), 7.48 (dd, J=2.5 and 8.7 Hz, 1H), 7.64 (d, J=2.5 Hz, 1H).

1. temperatureThen, the mixture was refluxed
2. temperatureunder heating for 1 hour
3. distillationThe solvent was distilled off from the reaction mixture
4. temperaturethe reaction mixture was cooled to 0° C.
5. dissolutiondissolved in toluene (10 ml)
6. customto have room temperature
7. stirringit was stirred for 1 hour
8. temperatureThen, the mixture was refluxed
9. temperatureunder heating for 2 hours
10. customAfter completion of the reaction
11. extractionthe mixture was extracted with ethyl acetate (10 ml×2)
12. washAn organic layer was washed with water (10 ml×3)
13. dry with materialdried over anhydrous magnesium sulfate
14. filtrationfiltered
15. customto remove a desiccant, and the solvent
16. distillationwas distilled off from the filtrate under reduced pressure
17. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/10)