Chlorodifluoromethane → 1-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester

HRID 915482Notes

Reaction equation

HRID 915482 reaction equation
Cl[CH:2]([F:4])[F:3].[CH2:5]([O:7][C:8]([C:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[NH:12][N:11]=1)=[O:9])[CH3:6].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:5]([O:7][C:8]([C:10]1[N:11]([CH:2]([F:4])[F:3])[N:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH:14]=1)=[O:9])[CH3:6].[CH2:5]([O:7][C:8]([C:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[N:12]([CH:2]([F:4])[F:3])[N:11]=1)=[O:9])[CH3:6]

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 11430Potassium CarbonateHCID 178468641HCID 178468641, compound

Product 2

HCID 674016321-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl esterYield 55%HCID 674025302-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-2H-pyrazole-3-carboxylic acid ethyl esterYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Chlorodifluoromethane (28.6 g, 331 mmol) was introduced to a suspension of 5-(4-trifluoromethoxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (2 g, 7 mmol; example 11 b]) and anhydrous potassium carbonate (2.76 g, 20 mmol) in dry N,N-dimethylformamide (120 ml) at 90° C. for 2 h. After cooling, the mixture was poured into ice water (400 ml) and extracted four times with dichloromethane. The combined extracts were washed two times with ice water/brine and dried over sodium sulfate. The solvent was removed under reduced pressure to give a yellow solid which was purified by column chromatography (silica gel, heptane/AcOEt) to give 281 mg (0.8 mmol, 12%) 2-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester as white solid and 1.29 g (3.7 mmol, 55%) 1-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester as white solid.

Workup

  1. temperatureAfter cooling
  2. extractionextracted four times with dichloromethane
  3. washThe combined extracts were washed two times with ice water/brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customto give a yellow solid which
  7. customwas purified by column chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-ea7e2f404be8441aba885d6bec5a731a
Source dataset
uspto-grants-2007_09
Patent number
US07265149B2

Reaction notes

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