Hydrochloric Acid → ethyl 3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylate

HRID 2391118Notes

Reaction equation

HRID 2391118 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[NH:6][N:5]=1.FC(F)(F)S(O[CH2:20][C:21]([F:24])([F:23])[F:22])(=O)=O.Cl>CN(C)C=O>[CH3:3][C:4]1[CH:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:6]([CH2:20][C:21]([F:24])([F:23])[F:22])[N:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 178469061HCID 178469061, compound

Product 1

HCID 57441025ethyl 3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylateYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (1.62 g, 40.4 mmol) in N,N-dimethylformamide (250 mL) was added dropwise a solution of ethyl 3-methyl-1H-pyrazole-5-carboxylate (5660 mg, 36.8 mmol) in N,N-dimethylformamide (50 mL) over 10 min under ice-cooling. After the completion of the dropwise addition, the reaction mixture was stirred at 0° C. for 10 min and at room temperature for 40 min. To the mixture was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (9.87 g, 40.4 mmol), and the mixture was stirred at room temperature for 3 hr. Under ice-cooling, 1N hydrochloric acid (36 mL) was added to the mixture, and the solvent was evaporated under reduced pressure. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the residue, and the aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran. Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→60/40), and recrystallized from ethyl acetate/hexane to give ethyl 3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylate (1.98 g, 23%) as white crystals.

Workup

  1. temperaturecooling
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 3 hr
  4. temperatureUnder ice-cooling
  5. customthe solvent was evaporated under reduced pressure
  6. additionEthyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the residue
  7. extractionthe aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran
  8. washCombined organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltrated
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→60/40)
  13. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-d09dcb5535b94cb9a5051a42dc8ac22b
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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