Dimethylformamide → 5-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde

HRID 1172115Notes

Reaction equation

HRID 1172115 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][N:7]([CH3:10])C=O.[F:11][CH:12]([F:20])[C:13]1[CH:17]=[C:16]([OH:18])N(C)[N:14]=1>O>[Cl:3][C:10]1[N:7]([CH3:6])[N:14]=[C:13]([CH:12]([F:20])[F:11])[C:17]=1[CH:16]=[O:18]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178481857HCID 178481857, compound

Product 1

HCID 197546925-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehydeYield 73.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

41.6 g (270.1 mmoles) of phosphorus oxychloride was added, with ice-cooling, to 7.9 g (108.0 mmoles) of N,N-dimethylformamide. Thereto was added, at room temperature, 8.0 g (54.0 mmoles) of 3-difluoromethyl-1-methyl-1H-pyrazol-5-ol. The mixture was refluxed for 4 hours with heating, to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water, followed by extraction with chloroform. The resulting organic layer was washed with water, a 5% aqueous sodium hydroxide solution and water in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to vacuum distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate mixed solvent) to obtain 7.7 g (yield: 73.3%) of 5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole-4-carboaldehyde as white crystals.

Workup

  1. additionThereto was added, at room temperature
  2. temperatureThe mixture was refluxed for 4 hours
  3. temperaturewith heating
  4. customto give rise
  5. customto a reaction
  6. customAfter the completion of the reaction
  7. extractionfollowed by extraction with chloroform
  8. washThe resulting organic layer was washed with water
  9. dry with materiala 5% aqueous sodium hydroxide solution and water in this order and then dried over anhydrous magnesium sulfate
  10. distillationThe resulting solution was subjected to vacuum distillation
  11. customto remove the solvent
  12. customThe residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate mixed solvent)

Sources & evidence

ORD record
ord-4637ba52a60d4f73a759938b892d7d75
Source dataset
uspto-grants-2010_11
Patent number
US07833939B2

Reaction notes

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