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

HRID 731672Notes

Reaction equation

HRID 731672 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>ClCCl.[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>[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 71%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

3-Bromo-2-chloro-6-fluorotoluene (7.0 g, 31 mmol), zinc cyanide (3.7 g, 31 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.81 g, 1.56 mmol) was added to a flask under argon atmosphere. Dry DMF (35 mL) was added and the reaction mixture was stirred under argon at 120° C. The reaction was monitored by GC-MS and full conversion was observed after 2 hours. The mixture was diluted with dichloromethane (300 mL), washed with water (100 mL) and 4% magnesium sulfate solution (100 mL), dried over magnesium sulphate, filtered, and evaporated to give a clear oil. The product was further purified by column chromatography on silica gel using n-heptane/ethyl acetate (9:1) giving a white solid (3.79 g, 71%).

Workup

  1. washwashed with water (100 mL) and 4% magnesium sulfate solution (100 mL)
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated
  5. customto give a clear oil
  6. customThe product was further purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-9f11736a72414282bbbe5e4668346491
Source dataset
uspto-grants-2009_09
Patent number
US07585877B2

Reaction notes

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