Dimethylformamide → 2-(2-Bromo-4-fluorophenyl)-2-methylpropanenitrile

HRID 558114Notes

Reaction equation

HRID 558114 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[CH2:11][C:12]#N.[CH3:14]I.C[N:17]([CH3:20])C=O>>[Br:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]([CH3:12])([CH3:14])[C:20]#[N:17]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 8263922-(2-Bromo-4-fluorophenyl)acetonitrile

Product 1

HCID 574450632-(2-Bromo-4-fluorophenyl)-2-methylpropanenitrileYield 65%

Procedure

Add sodium hydride (1 g, 42.1 mmol) to a stirred solution of (2-bromo-4-fluoro-phenyl)-acetonitrile (3 g, 14 mmol) in 10 mL of dimethyl formamide (DMF) at 0° C. Stir the mixture at 0° C. to RT for half an hour. Add methyl iodide (6 g, 42 mmol). Stir for another 30 min. Quench the reaction with water. Extract the product into DCM. Dry the organic phase over sodium sulfate and concentrate to give an oily residue. Purify the residue by flash column chromatography (FCC) (hexane to 20% ethyl acetate in hexane as gradient elute) to give the title compound as a white solid (2.2 g, 65%). 1H NMR (400 MHz, CDCl3) δ 7.41-7.47 (m, 2H), 7.03-7.08 (m, 1H), 1.88 (s, 6H).

Workup

  1. stirringStir for another 30 min
  2. customQuench
  3. customthe reaction with water
  4. extractionExtract the product into DCM
  5. dry with materialDry the organic phase over sodium sulfate
  6. concentrationconcentrate
  7. customto give an oily residue
  8. customPurify the residue
  9. washby flash column chromatography (FCC) (hexane to 20% ethyl acetate in hexane as gradient elute)

Sources & evidence

ORD record
ord-4ac5131a912940589268aad25d8e388d
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

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