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

HRID 2359076Notes

Reaction equation

HRID 2359076 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+].[CH2:14](I)[CH2:15][CH3:16].O>CN(C)C=O.CC(OC)(C)C>[CH3:1][C:2]1[CH:3]=[C:4]([C:7]2[CH:11]=[CH:10][N:9]([CH2:14][CH2:15][CH3:16])[N:8]=2)[S:5][CH:6]=1.[CH3:1][C:2]1[CH:3]=[C:4]([C:7]2[N:8]([CH2:14][CH2:15][CH3:16])[N:9]=[CH:10][CH:11]=2)[S:5][CH:6]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 178431894HCID 178431894, compound

Product 2

HCID 672606313-(4-methyl-2-thienyl)-1-propyl-1H-pyrazoleYield 74%HCID 672616685-(4-methyl-2-thienyl)-1-propyl-1H-pyrazoleYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

3-(4-methyl-2-thienyl)-1H-pyrazole (9.1 mmol) was dissolved in 20 mL dry N,N-dimethylformamide and cooled to 0° C. under argon atmosphere. Sodium hydride (13.7 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, propyl iodide (18.3 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 1.39 g 3-(4-methyl-2-thienyl)-1-propyl-1H-pyrazole (74% yield) and 341 mg of 5-(4-methyl-2-thienyl)-1-propyl-1H-pyrazole (18% 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-1ddaf21f3be3416db281ef601cc922cd
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

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