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

HRID 2387147Notes

Reaction equation

HRID 2387147 reaction equation
C[N:2]([CH:4]=O)[CH3:3].O=P(Cl)(Cl)[Cl:8].[F:11][CH:12]([F:20])[C:13]1[CH:17]=[C:16]([OH:18])N(C)[N:14]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[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

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 178481857HCID 178481857, compound

Product 1

HCID 197546925-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehydeYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To DMF (40.84 g, 0.56 mol) was added POCl3 (104.4 mL, 1.12 mol) at 0° C. After 30 min, to the resulting Vilsmier reagent was added 3-(difluoromethyl)-1-methyl-1H-pyrazol-5-ol from step 1 above (69.1 g, 0.46 mol), and the mixture was heated at 80° C. for 16 h. Then reaction was diluted with dichloromethane (400 mL), and treated with a solution of potassium carbonate (780 g) in water (2 L) at 0° C. The organic layer was separated, and the aqueous layer extracted with dichloromethane (3×100 mL). The combined organic extracts were washed with water (500 mL), passed through a layer of silica gel (10×10 cm), and evaporated. The residue was crystallized from ether (100 mL) and hexane (100 mL) to give 69 g (77%) of the title product.

Workup

  1. customThen reaction
  2. customThe organic layer was separated
  3. extractionthe aqueous layer extracted with dichloromethane (3×100 mL)
  4. washThe combined organic extracts were washed with water (500 mL)
  5. customevaporated
  6. customThe residue was crystallized from ether (100 mL) and hexane (100 mL)

Sources & evidence

ORD record
ord-74b30db41f5c455180ab47a91fec2849
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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