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

HRID 2359068Notes

Reaction equation

HRID 2359068 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+].[CH:13](I)([CH3:15])[CH3:14].O>CN(C)C=O.CC(OC)(C)C>[CH: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)([CH3:15])[CH3:14].[CH: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)([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 962WaterHCID 6362Isopropyl iodide2×HCID 24758Sodium hydrideHCID 178420845HCID 178420845, compound

Product 2

HCID 589771571-isopropyl-3-(2-thienyl)-1H-pyrazoleYield 88%HCID 598337391-isopropyl-5-(2-thienyl)-1H-pyrazoleYield 1%

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 dry 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, isopropyl iodide (47.4 mmol) was added dropwise at 0° C. The reaction mixture was stirred at room temperature for 14 h. Isopropyl iodide (5.9 mmol) was added and the mixture was stirred at room temperature overnight. 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 5.40 g 1-isopropyl-3-(2-thienyl)-1H-pyrazole (88% yield) and 50 mg of 1-isopropyl-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. stirringthe mixture was stirred at room temperature overnight
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with MTBE
  7. washThe combined organic extracts were successively washed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (toluene:ethyl acetate 100:0 to 0:100)

Sources & evidence

ORD record
ord-07d02b49259548c9b5b4fd9b2ba0217b
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

Loading…