Hydrochloric Acid → 3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole

HRID 644842Notes

Reaction equation

HRID 644842 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[C:15]1[C:20]([Cl:21])=[CH:19][C:18]([C:22]([F:25])([F:24])[F:23])=[CH:17][N:16]=1.Cl>CN(C=O)C>[Cl:21][C:20]1[C:15]([O:7][C:8]2[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=2)=[N:16][CH:17]=[C:18]([C:22]([F:24])([F:23])[F:25])[CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 1122342,3-Dichloro-5-(trifluoromethyl)pyridineHCID 3197713H-Pyrazol-3-one, 2,4-dihydro-5-methyl-

Product 1

HCID 178624573-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazoleYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Potassium carbonate (7.60 g, 55.0 mmol) was added to a solution of 3-hydroxy-5-methylpyrazole (4.90 g, 50.0 mmol) and 2,3-dichloro-5-trifluoromethylpyridine (10.8 g, 50.0 mmol) in DMF (50 ml) at room temperature, and the mixture was stirred under heating at 60° 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 (30 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=1/2), to give a white solid of 3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (10.5 g, yield: 76.0%). mp: 93-95° C.; 1H-NMR (CDCl3, TMS, ppm): δ 2.32 (s, 3H), 5.90 (s, 1H), 7.98 (d, J=2.0 Hz, 1H), 8.33 (m, 1H), 10.80-11.60 (br s, 1H).

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate (30 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=1/2)

Sources & evidence

ORD record
ord-e41bc377a4604567a4756ce158f3ef90
Source dataset
uspto-grants-2010_04
Patent number
US07700786B2

Reaction notes

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