Chloroacetonitrile → [4-(3-Acetyl-5-chloro-2-methoxy-6-methylphenyl)-1H-pyrazol-1-yl]acetonitrile

HRID 510906Notes

Reaction equation

HRID 510906 reaction equation
[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([C:13]2[CH:14]=[N:15][NH:16][CH:17]=2)[C:5]([O:11][CH3:12])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[H-].[Na+].Cl[CH2:22][C:23]#[N:24]>CN(C)C=O>[C:8]([C:6]1[C:5]([O:11][CH3:12])=[C:4]([C:13]2[CH:17]=[N:16][N:15]([CH2:22][C:23]#[N:24])[CH:14]=2)[C:3]([CH3:18])=[C:2]([Cl:1])[CH:7]=1)(=[O:10])[CH3:9]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 866668231-[5-Chloro-2-methoxy-4-methyl-3-(1H-pyrazol-4-yl)phenyl]ethanone

Product 1

HCID 86666824[4-(3-Acetyl-5-chloro-2-methoxy-6-methylphenyl)-1H-pyrazol-1-yl]acetonitrileYield 67.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[5-chloro-2-methoxy-4-methyl-3-(1H-pyrazol-4-yl)phenyl]ethanone (0.13 g, 0.49 mmol) in N,N-dimethylformamide (2 mL) was added sodium hydride (60% in oil, 0.014 g, 0.59 mmol) at 0° C. The mixture was stirred for 1 hour at room temperature, followed by the addition of chloroacetonitrile (0.037 mL, 0.59 mmol) at 0° C. The reaction was stirred at room temperature for 1 hour, quenched with water and extracted with ethyl acetate. The organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified on silica gel (eluting with 0-40% of ethyl acetate in hexanes) to afford the desired product (0.1 g, 67%). LCMS calculated for C15H15ClN3O2 (M+H)+: m/z=304.1. found: 304.1.

Workup

  1. stirringThe reaction was stirred at room temperature for 1 hour
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified on silica gel (eluting with 0-40% of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7fdf8a849caf43d4b832484efb6cbc37
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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