Dimethylformamide → 2-Chloro-4-fluoro-3-methylbenzonitrile

HRID 731671Notes

Reaction equation

HRID 731671 reaction equation
Br[C:2]1[C:3]([Cl:10])=[C:4]([CH3:9])[C:5]([F:8])=[CH:6][CH:7]=1.[CH3:11][N:12](C=O)C>[C-]#N.[Zn+2].[C-]#N.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(OCC)C>[Cl:10][C:3]1[C:4]([CH3:9])=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[C:11]#[N:12]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 27362273-Bromo-2-chloro-6-fluorotoluene

Product 1

HCID 445509712-Chloro-4-fluoro-3-methylbenzonitrileYield 42%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

3-Bromo-2-chloro-6-fluorotoluene 165RL91 (173 mg, 0.78 mmol), zinc cyanide (91 mg, 0.78 mmol) and tetrakis(triphenylphosphine)palladium(0) (27 mg, 23 μmol) was charged in a vial, DMF (1 mL) added, and the mixture irradiated for 150 sec at 200° C. in a microwave oven. Diethyl ether (30 ml) was added and the reaction mixture washed with magnesium sulphate (4% solution, 3×20 mL) followed by brine (20 mL). The organic layer was dried and evaporated. The product was further purified by column chromatography on silica gel using n-heptane/ethyl acetate (9:1) giving a white solid (55 mg, 42%).

Workup

  1. additionadded
  2. customthe mixture irradiated for 150 sec at 200° C. in a microwave oven
  3. washthe reaction mixture washed with magnesium sulphate (4% solution, 3×20 mL)
  4. customThe organic layer was dried
  5. customevaporated
  6. customThe product was further purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-805edac049ee4db6b9d578a9e03cf646
Source dataset
uspto-grants-2009_09
Patent number
US07585877B2

Reaction notes

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