Dimethylformamide → 2-Fluoro-4-methylbenzonitrile

HRID 277769Notes

Reaction equation

HRID 277769 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9].[CH3:10][N:11](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.CCOC(C)=O>[C:10]([C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9])#[N:11]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 5732804-Bromo-3-fluorotoluene

Product 1

HCID 27784432-Fluoro-4-methylbenzonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 4-bromo-3-fluorotoluene (50.0 g, 264 mmol) in 500 mnL 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-1fce1789e11846028186549d055ec612
Source dataset
uspto-grants-2002_03
Patent number
US06358956B1

Reaction notes

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