Dimethylformamide → 3-Chloro-5-fluorobenzonitrile

HRID 431882

Reaction equation

HRID 431882 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Cl:9])[CH:3]=1.ClCCl.[CH3:13][N:14](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.Cl[Pd]Cl.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]>[Cl:9][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=1)[C:13]#[N:14]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 27362231-Bromo-3-chloro-5-fluorobenzene

Product 1

HCID 27348413-Chloro-5-fluorobenzonitrileYield 85%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-bromo-3-chloro-5-fluorobenzene (25.0 g, 120 mmol), zinc cyanide (8.45 g, 72 mmol) zinc (dust, 235 mg, 3.6 mmol), [1,1′Bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane (1:1) (1.5 g, 1.8 mmol) in N,N-dimethylformamide (70 ml) was heated at reflux for 1 hour. After cooling the reaction was diluted with ethyl acetate and extracted with water and brine. Silica gel chromatography afforded 15.9g (85%) 3-chloro-5-fluorobenzonitrile.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. temperatureAfter cooling the reaction
  4. extractionextracted with water and brine

Sources & evidence

ORD record
ord-fe64569d0052442c86fc9381718ba59e
Source dataset
uspto-grants-2003_12
Patent number
US06660753B2

Linked notes

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