Dimethylformamide → 2-Chloro-4-fluoro-5-methylbenzonitrile

HRID 2046641Notes

Reaction equation

HRID 2046641 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][C:3]=1[Cl:10].[CH3:11][N:12](C)C=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[Cl:10][C:3]1[CH:4]=[C:5]([F:9])[C:6]([CH3:8])=[CH:7][C:2]=1[C:11]#[N:12]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 27732735-Bromo-4-chloro-2-fluorotoluene

Product 1

HCID 569655632-Chloro-4-fluoro-5-methylbenzonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

Under an argon atmosphere, to a solution (20 mL) of 1-bromo-2-chloro-4-fluoro-5-methylbenzene (4.47 g) in N,N-dimethylformamide were added tetrakis(triphenylphosphine)palladium(0) (0.78 g) and zinc cyanide (1.23 g). The mixture was stirred at 110° C. for 13 hr and partitioned between ethyl acetate-water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate) and crystallized from ethyl acetate-hexane to give the title compound as a colorless solid (yield: 2.3 g).

Workup

  1. custompartitioned between ethyl acetate-water
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate)
  6. customcrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-a011613a45d34205a01bf600aa9ec2e7
Source dataset
uspto-grants-2013_11
Patent number
US08592452B2

Reaction notes

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