Water → 1-ethyl-3-(2-thienyl)-1H-pyrazole

HRID 2359069Notes

Reaction equation

HRID 2359069 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:10]=[CH:9][NH:8][N:7]=1.[H-].[Na+].[CH2:13](I)[CH3:14].O>CN(C)C=O.CC(OC)(C)C>[CH2:13]([N:8]1[CH:9]=[CH:10][C:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[N:7]1)[CH3:14].[CH2:13]([N:7]1[C:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:9]=[N:8]1)[CH3:14]

Participants

8

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178420845HCID 178420845, compound

Product 2

HCID 672602691-ethyl-5-(2-thienyl)-1H-pyrazoleYield 1%HCID 672609041-ethyl-3-(2-thienyl)-1H-pyrazoleYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

3-(2-thienyl)-1H-pyrazole (31.6 mmol) was dissolved in 150 mL N,N-dimethylformamide and cooled to 0° C. under argon atmosphere. Sodium hydride (37.9 mmol, 60% dispersion in mineral oil) was added in portions at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred at room temperature for 15 min. After cooling to 0° C. again, ethyl iodide (47.4 mmol) was added dropwise at 0° C. The reaction mixture was stirred at room temperature for 14 h. Water and MTBE were added to the reaction mixture. The phases were separated and the aqueous phase was extracted with MTBE. The combined organic extracts were successively washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (toluene:ethyl acetate 100:0 to 0:100) to afford 2.50 g 1-ethyl-3-(2-thienyl)-1H-pyrazole (44% yield) and 50 mg of 1-ethyl-5-(2-thienyl)-1H-pyrazole (1% yield).

Workup

  1. temperatureto warm to room temperature
  2. temperatureAfter cooling to 0° C. again
  3. stirringThe reaction mixture was stirred at room temperature for 14 h
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with MTBE
  6. washThe combined organic extracts were successively washed with water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel (toluene:ethyl acetate 100:0 to 0:100)

Sources & evidence

ORD record
ord-cb92d2b101ff4dc2907c5f498c0c58c4
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

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