Potassium Carbonate → Ethyl 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 2236187Notes

Reaction equation

HRID 2236187 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([C:11]([F:14])([F:13])[F:12])=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].I[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[C:7]([C:11]([F:13])([F:14])[F:12])=[N:8][N:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178469923HCID 178469923, compound

Product 1

HCID 11448972Ethyl 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylateYield 82.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.25 g, 6.0 mmol), copper (I) iodide (0.342 g, 1.8 mmol) and potassium carbonate (0.58 g, 4.2 mmol) in toluene (6 mL) in a round bottom flask was purged with argon. To the reaction mixture was then added iodobenzene (0.81 mL, 7.2 mmol) and racemic trans-N,N′-dimethyl-cyclohexane-1,2-diamine (0.58 mL, 3.6 mmol). The slurry was heated under Ar in an oil bath at 110° C. for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through a bed of celite. After washing the celite with ethyl acetate, the filtrates were combined and concentrated to give a crude which was purified by silica gel chromatography (Isco 120 g column, 0 to 30% ethyl acetate/hexanes) to give 1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.40 g, 82%) as an off-white solid. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. customwas purged with argon
  2. temperatureAfter cooling to room temperature
  3. filtrationfiltered through a bed of celite
  4. washAfter washing the celite with ethyl acetate
  5. concentrationconcentrated
  6. customto give a crude which
  7. customwas purified by silica gel chromatography (Isco 120 g column, 0 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-80716ec451cd4478a06768c69386eb0b
Source dataset
uspto-grants-2010_05
Patent number
US07714126B2

Reaction notes

Loading…