Triethylamine → N-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide

HRID 644904Notes

Reaction equation

HRID 644904 reaction equation
Cl[C:2](OC(Cl)(Cl)Cl)=[O:3].[Cl:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([F:20])[C:11]=1[O:21][C:22]1[CH:26]=[C:25]([CH3:27])[NH:24][N:23]=1.[CH2:28]([NH2:34])[CH:29]1[O:33][CH2:32][CH2:31][CH2:30]1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:28]([NH:34][C:2]([N:24]1[C:25]([CH3:27])=[CH:26][C:22]([O:21][C:11]2[C:12]([F:20])=[CH:13][C:14]([C:16]([F:19])([F:17])[F:18])=[CH:15][C:10]=2[Cl:9])=[N:23]1)=[O:3])[CH:29]1[O:33][CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 253298TetrahydrofurfurylamineHCID 178624283-(2-Chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole

Product 1

HCID 17862429N-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamideYield 29.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e28ee6ab2d83466c9dbc838ab199698c
Source dataset
uspto-grants-2010_04
Patent number
US07700786B2

Reaction notes

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