Dichloromethane → 2-(2,2,2-Trifluoro-ethyl)-5-(4-trifluoromethyl-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester

HRID 915438Notes

Reaction equation

HRID 915438 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[NH:10][N:9]=1)=[O:7])[CH3:4].[F:23][C:24]([F:35])([F:34])[CH2:25]OS(C(F)(F)F)(=O)=O.ClCCl>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH2:25][C:24]([F:35])([F:34])[F:23])[N:10]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][CH:14]=2)[CH:12]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 178468625HCID 178468625, compound

Product 1

HCID 866006252-(2,2,2-Trifluoro-ethyl)-5-(4-trifluoromethyl-phenyl)-2H-pyrazole-3-carboxylic acid ethyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (55% dispersion in mineral oil, 203 mg, 5 mmol) was added to an ice cooled solution of 5-(4-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (1 g, 4 mmol; PCT Int. Appl. (2003), WO 2004000785 A2) in DMF (60 ml) under an argon atmosphere. The solution was stirred for 10 min at 0° C. and for 40 min at ambient temperature. Trifluoroethyltriflate (1.07 g, 5 mmol) was added and the mixture was stirred for 3 h at ambient temperature. The solution was cooled to 0° C., 1 N HCl/ice water 1/2 and dichloromethane were added. The aqueous layer was extracted two times with dichloromethane, the combined extracts were washed with brine/ice water 1/1 and dried over sodium sulfate. Evaporation of the solvent under reduced pressure gave yellow crystals which were purified by column chromatography (silica gel, n-heptane/AcOEt) to yield 833 mg (2.27 mmol, 65%) of the title compound as colorless crystals.

Workup

  1. stirringthe mixture was stirred for 3 h at ambient temperature
  2. temperatureThe solution was cooled to 0° C.
  3. extractionThe aqueous layer was extracted two times with dichloromethane
  4. washthe combined extracts were washed with brine/ice water 1/1
  5. dry with materialdried over sodium sulfate
  6. customEvaporation of the solvent under reduced pressure
  7. customgave yellow crystals which
  8. customwere purified by column chromatography (silica gel, n-heptane/AcOEt)

Sources & evidence

ORD record
ord-82214de6e58345a5ad49579ca6eb74b3
Source dataset
uspto-grants-2007_09
Patent number
US07265149B2

Reaction notes

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