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

HRID 2359966Notes

Reaction equation

HRID 2359966 reaction equation
C[N:2]([CH:4]=O)[CH3:3].P(Cl)(Cl)([Cl:8])=O.[F:11][CH:12]([F:20])[C:13]1[CH2:17][C:16](=[O:18])N(C)[N:14]=1>>[Cl:8][C:4]1[N:2]([CH3:3])[N:14]=[C:13]([CH:12]([F:20])[F:11])[C:17]=1[CH:16]=[O:18]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 62880533HCID 62880533, compound

Product 1

HCID 197546925-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehydeYield 78.2%

Conditions

Temperature
120 °C

Procedure

DMF (9.5 mL, 0.12 mol) was stirred over ice bath and phosphoryl chloride (24.0 mL, 0.257 mol) was added dropwise. To the solution was added 3-(difluoromethyl)-1-methyl-1H-pyrazol-5(4H)-one (5.51 g, 0.0372 mol) portion wise and the mixture was heated at 120° C. for 40 minutes. The reaction mixture was cooled, and the phosphoryl chloride was quenched by adding small chunks of ice slowly with stirring. The mixture was then extracted with ethyl acetate three times and combined organic layer was washed with water and brine, dried over MgSO4 and evaporated to give 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde (5.66 g, 78.2%) as a dark orange/brown solid. This material was used without further purification for the next reaction.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe phosphoryl chloride was quenched
  3. additionby adding small chunks of ice slowly
  4. extractionThe mixture was then extracted with ethyl acetate three times
  5. washwas washed with water and brine
  6. dry with materialdried over MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-097a094ac52b46fca75ba09d0029cd58
Source dataset
uspto-grants-2014_04
Patent number
US08686018B2

Reaction notes

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