Hydrochloric Acid → 3-(2-Chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole

HRID 644838Notes

Reaction equation

HRID 644838 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=1.[Cl:14][C:15]1[CH:16]=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:18]=[C:19]([F:22])[C:20]=1F.Cl>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([C:23]([F:24])([F:25])[F:26])[CH:18]=[C:19]([F:22])[C:20]=1[O:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 3197713H-Pyrazol-3-one, 2,4-dihydro-5-methyl-HCID 2736496Benzene, 1-chloro-2,3-difluoro-5-(trifluoromethyl)-

Product 1

HCID 178624283-(2-Chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazoleYield 33.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Potassium carbonate (1.66 g, 12 mmol) was added to a solution of 3-hydroxy-5-methylpyrazole (2.45 g, 25.0 mmol) and 3-chloro-4,5-difluorobenzotrifluoride (2.5 g, 25.0 mmol) in DMF (40 ml), and the mixture was stirred under heating at 70° C. for 4 hours. After completion of the reaction, the reaction mixture was poured into 2N hydrochloric acid (100 ml) and extracted with ethyl acetate (50 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=1/5), to give a white solid of 3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (2.29 g, yield: 33.8%). mp: 171-174° C.; 1H-NMR (CDCl3, TMS, ppm): δ 2.27 (s, 3H), 5.71 (s, 1H), 7.37 (dd, JHF=1.8 and 9.4 Hz, 1H), 7.54 (s, 1H), 8.85-9.55 (br s, 1H).

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate (50 ml×3)
  3. washAn organic layer was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customto remove a desiccant, and the solvent
  7. distillationwas distilled off from the filtrate under reduced pressure
  8. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/5)

Sources & evidence

ORD record
ord-bbe9b8563ab547a88383120e0eba40e2
Source dataset
uspto-grants-2010_04
Patent number
US07700786B2

Reaction notes

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