Toluene → 2-Fluoro-4-methylbenzonitrile

HRID 2306167Notes

Reaction equation

HRID 2306167 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9].C1(C)C=CC=CC=1.[CH3:17][N:18](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:17]([C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9])#[N:18]

Participants

6

Reactant 3

HCID 1140TolueneHCID 6228DimethylformamideHCID 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
100 °C

Procedure

To a deoxygenated solution of 4-bromo-3-fluorotoluene (25.0 g, 132 mmol) in DMF (500 mL) was added Zn(CN)2 (10.1 g, 86 mmol) and Pd(PPh3)4 (15 g, 13 mmol). The reaction was stirred at 100° C. for 18 hours, then cooled to room temperature. The solution was poured into toluene (1 L), washed with 30% aqueous NH4OH (2×1 L), then brine (800 mL), then dried (Na2SO4), filtered, and concentrated in vacuo to provide the crude product. Purification by silica gel chromatography, eluting with a gradient of hexane −0% to 7% EtOAc, yielded the titled product.

Workup

  1. temperaturecooled to room temperature
  2. washwashed with 30% aqueous NH4OH (2×1 L)
  3. dry with materialbrine (800 mL), then dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide the crude product
  7. customPurification by silica gel chromatography
  8. washeluting with a gradient of hexane −0% to 7% EtOAc

Sources & evidence

ORD record
ord-ddf8910b6de54a2aab1286dcb62521d5
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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