Water → 1-methyl-3-(4-methyl-2-thienyl)-1H-pyrazole

HRID 2359074Notes

Reaction equation

HRID 2359074 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:7]2[CH:11]=[CH:10][NH:9][N:8]=2)[S:5][CH:6]=1.[H-].[Na+].[CH3:14]I.O>CN(C)C=O.CC(OC)(C)C>[CH3:14][N:9]1[CH:10]=[CH:11][C:7]([C:4]2[S:5][CH:6]=[C:2]([CH3:1])[CH:3]=2)=[N:8]1.[CH3:14][N:8]1[C:7]([C:4]2[S:5][CH:6]=[C:2]([CH3:1])[CH:3]=2)=[CH:11][CH:10]=[N:9]1

Participants

8

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178431894HCID 178431894, compound

Product 2

HCID 672616091-methyl-3-(4-methyl-2-thienyl)-1H-pyrazoleYield 54%HCID 672617041-methyl-5-(4-methyl-2-thienyl)-1H-pyrazoleYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

3-(4-methyl-2-thienyl)-1H-pyrazole (9.0 mmol) was dissolved in 20 mL dry N,N-dimethylformamide and cooled to 0° C. under argon atmosphere. Sodium hydride (13.5 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, methyl iodide (18.0 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 (dichloromethane:MTBE 100:0 to 90:10) to afford 864 mg 1-methyl-3-(4-methyl-2-thienyl)-1H-pyrazole (54% yield) and 480 mg of 1-methyl-5-(4-methyl-2-thienyl)-1H-pyrazole (30% 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 (dichloromethane:MTBE 100:0 to 90:10)

Sources & evidence

ORD record
ord-46922a7119ea47109cffdd27215d93f8
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

Loading…