Chloroacetonitrile → 1-Cyanomethyl-3-(2,6-difluorophenyl)pyrazole

HRID 990726Notes

Reaction equation

HRID 990726 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:13]=[CH:12][NH:11][N:10]=1.Cl[CH2:15][C:16]#[N:17].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:16]([CH2:15][N:11]1[CH:12]=[CH:13][C:9]([C:3]2[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[N:10]1)#[N:17]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 178505719HCID 178505719, compound

Product 1

HCID 221694981-Cyanomethyl-3-(2,6-difluorophenyl)pyrazoleYield 47.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3.0 g of 3-(2,6-difluorophenyl)pyrazole was dissolved in 20 ml of acetonitrile, and 2.52 g of chloroacetonitrile and 4.61 g of potassium carbonate were added thereto at room temperature, and heated under reflux for 5 hours. After acetonitrile was distilled off under reduced pressure, ethyl acetate was added to the residue, which was then washed with a small amount of water. The organic layer was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residual product was recrystallized from a mixed solvent of isopropylether and diethyl ether to obtain 1.74 g of l-cyanomethyl-3-(2,6-difluorophenyl)pyrazole. 2) A solution of 0.5 g of 1-cyanomethyl-3-(2,6-difluorophenyl)pyrazole dissolved in 10 ml of THF was dropwise added to a suspension of 0.15 g of 55% sodium hydride in 10 ml of THF, at; 50° C. After the resulting product was stirred for 30 minutes, a solution of 0.67 g of 1-(1-methyl-3,5-dichloropyrazole-4-carbonyl)pyrazole dissolved in 10 ml of THF was dropwise added thereto at 50° C. and then stirred overnight at room temperature. The reaction mixture was poured into water, then extracted with ethyl acetate and washed with a small amount of water. The resulting product was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residual product was recrystallized from a mixed solvent of isopropyl ether/ethyl acetate=3/1 to obtain 0.52 g of 2-(3-(2,6-difluorophenyl)pyrazol-1-yl)-3-(1-methyl-3,5-dichloropyrazol-4-yl)-3-hydroxyacrylonitrile.

Workup

  1. temperatureunder reflux for 5 hours
  2. distillationAfter acetonitrile was distilled off under reduced pressure, ethyl acetate
  3. additionwas added to the residue, which
  4. washwas then washed with a small amount of water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residual product was recrystallized from a mixed solvent of isopropylether and diethyl ether

Sources & evidence

ORD record
ord-cbde62cfc1f34d47bf41cfe0213fdf8c
Source dataset
uspto-grants-2002_10
Patent number
US06462049B1

Reaction notes

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