Trimethylsilyl cyanide → 2-(3-Chloro-2-fluorophenyl)acetonitrile

HRID 2277577Notes

Reaction equation

HRID 2277577 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Br)[C:3]=1[F:10].C[Si]([C:15]#[N:16])(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CC#N>[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH2:8][C:15]#[N:16])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 82115Trimethylsilyl cyanideHCID 5228271-(Bromomethyl)-3-chloro-2-fluorobenzeneHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 27737242-(3-Chloro-2-fluorophenyl)acetonitrileYield 88%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-chloro-3-bromomethyl-2-fluoro-benzene (2.22 g, 10 mmol) in CH3CN (30 mL) was added trimethylsilyl cyanide (1.5 mL) and TBAF (1M in THF, 12 mmol, 12 mL). The resulting reaction mixture was heated at reflux temperature for 30 min. After cooling to room temperature, the volatiles were evaporated under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was then washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to give the title compound (1.48 g, 88%). MS: 170.1 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux temperature for 30 min
  4. customthe volatiles were evaporated under reduced pressure
  5. customThe residue was partitioned between EtOAc and water
  6. washThe organic layer was then washed with brine
  7. customdried over anhy
  8. filtrationNa2SO4, filtered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-e99838d0abde499188cad416617c0b87
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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