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

HRID 2283190Notes

Reaction equation

HRID 2283190 reaction equation
[F:1][CH:2]([F:10])[C:3]1[CH:7]=[C:6](O)[N:5]([CH3:9])[N:4]=1.CN(C)[CH:13]=[O:14].P(Cl)(Cl)([Cl:18])=O>C1(C)C=CC=CC=1>[Cl:18][C:6]1[N:5]([CH3:9])[N:4]=[C:3]([CH:2]([F:10])[F:1])[C:7]=1[CH:13]=[O:14]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178481857HCID 178481857, compound

Product 1

HCID 197546925-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 137.5 g (929 mmol) of 3-(difluoromethyl)-1-methyl-1H-pyrazol-5-ol in 136 ml (1858 mmol) of dimethylformamide and 750 ml of toluene was added dropwise with cooling 571 g (3716 mmol) of phosphoryl chloride. The mixture was heated for 3 hours under reflux and allowed to cool, and the reaction mixture wash carefully poured into 41 of ice water. The product was extracted three times, each time with 1500 ml of ethyl acetate, and the combined organic phases were washed twice with saturated sodium bicarbonate solution and finally with saturated sodium chloride solution, dried over sodium sulphate and concentrated. 138 g (with a purity of >99% (GC)) of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde (II-1) in the form of a yellow-brown solid was obtained, which was used without further purification in the next reaction step.

Workup

  1. temperatureThe mixture was heated for 3 hours
  2. temperatureunder reflux
  3. temperatureto cool
  4. washthe reaction mixture wash carefully
  5. additionpoured into 41 of ice water
  6. extractionThe product was extracted three times
  7. washeach time with 1500 ml of ethyl acetate, and the combined organic phases were washed twice with saturated sodium bicarbonate solution and finally with saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-feb4abdff4b04b9c9d82e0d3a95b0f0f
Source dataset
uspto-grants-2015_09
Patent number
US09145369B2

Reaction notes

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