Dimethylformamide → 2-Fluoro-4-methylbenzonitrile

HRID 1987339Notes

Reaction equation

HRID 1987339 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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:9][C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[C:10]#[N:11]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 5732804-Bromo-3-fluorotoluene

Product 1

HCID 27784432-Fluoro-4-methylbenzonitrileYield 65%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

Under N2, to a suspension of 1-bromo-2-fluoro-4-methyl-benzene (2.59 g, 13.7 mmol) and Zn(CN)2 (1.60 g, 13.7 mmol) in dry DMF (50 mL) was added 1,1′-bis(diphenylphosphino)ferrocene (DPPF) (0.0753 g, 0.136 mmol) and Pd2(dba)3 (dba=di(benzylidene)acetone) (0.0623 g, 0.0681 mmol). After the mixture was heated at 130° C. for 2 days, the solvent was removed by evaporation under vacuum, and saturated aqueous NaHCO3 (40 mL) was added. The aqueous suspension was extracted with CH2Cl2 (3×40 mL), and the extract was dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residual solid was purified by flash chromatography on silica gel (1:20 EtOAc/hexanes), affording 2-fluoro-4-methyl-benzonitrile as a pale yellow solid (1.21 g, 65%). 1H NMR (CDCl3) δ 2.43 (s, 3H), 7.01-7.07 (m, 2H), 7.48-7.52 (m, 1H).

Workup

  1. customthe solvent was removed by evaporation under vacuum, and saturated aqueous NaHCO3 (40 mL)
  2. additionwas added
  3. extractionThe aqueous suspension was extracted with CH2Cl2 (3×40 mL)
  4. dry with materialthe extract was dried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed by evaporation under vacuum
  7. customthe residual solid was purified by flash chromatography on silica gel (1:20 EtOAc/hexanes)

Sources & evidence

ORD record
ord-dfd40acccf6148e19d2571a6260c623e
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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