Dimethylformamide → 2-Fluoro-4-methylbenzonitrile

HRID 2268796Notes

Reaction equation

HRID 2268796 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9].CCOC(C)=O.[CH3:16][N:17](C=O)C>[C-]#N.[C-]#N.[Zn+2].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:16]([C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9])#[N:17]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 5732804-Bromo-3-fluorotoluene

Product 1

HCID 27784432-Fluoro-4-methylbenzonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 4-bromo-3-fluorotoluene (50.0 g, 264 mmol) in 500 mL of DMF was added Zn(CN)2 (18.6 g, 159 mmol) and Pd(PPh3)4 (6.1 g, 5.3 mmol). The reaction was stirred at 80° C. for 6 hours, then cooled to room temperature. The solution was poured into EtOAc, washed with water, sat. aq. NaHCO3, and brine, then dried (Na2SO4), filtered, and concentrated in vacuo to provide the crude product. Purification by silica gel chromatography (0-5% EtOAc/hexane) provided the titled product.

Workup

  1. temperaturecooled to room temperature
  2. washwashed with water, sat. aq. NaHCO3, and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide the crude product
  7. customPurification by silica gel chromatography (0-5% EtOAc/hexane)

Sources & evidence

ORD record
ord-ef0d508774c344d3b69d9fd72ade043f
Source dataset
uspto-grants-2001_12
Patent number
US06329376B1

Reaction notes

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