4-Bromo-2-fluoroanisole → 3-Fluoro-4-methoxybenzonitrile

HRID 358807

Reaction equation

HRID 358807 reaction equation
[F:1][C:2]1[CH:7]=[C:6](Br)[CH:5]=[CH:4][C:3]=1[O:9][CH3:10].[Cu](C#N)[C:12]#[N:13]>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[O:9][CH3:10])[C:12]#[N:13]

Participants

5

Reactant 2

HCID 753784-Bromo-2-fluoroanisoleHCID 178418260HCID 178418260, compound

Product 1

HCID 27745483-Fluoro-4-methoxybenzonitrileYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

20 g of the 2-fluoro-4-bromoanisole thus obtained and 9.8 g of copper cyanide were dissolved in 100 ml of dimethyl formamide and heated under reflux for ten hours. To the reaction mixture, was added an aqueous solution of 20 g of ferric chloride in 100 ml of water. The reaction mixture was allowed to cool to room temperature and the reaction product was extracted with toluene. The organic layer was successively washed with water, a saturated aqueous solution of sodium carbonate and a saturated aqueous solution of common salt. Then the organic layer was separated. The extract was dried over anhydrous sodium sulfate and the solvent was distilled off. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate 10:1) and further recrystallized from ethanol. Thus 10.0 g of 3-fluoro-4-methoxybenzonitrile was obtained. Yield: 68%.

Workup

  1. temperatureheated
  2. temperatureunder reflux for ten hours
  3. extractionthe reaction product was extracted with toluene
  4. washThe organic layer was successively washed with water
  5. customThen the organic layer was separated
  6. dry with materialThe extract was dried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off
  8. customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate 10:1)
  9. customfurther recrystallized from ethanol

Sources & evidence

ORD record
ord-d3fc8bc045b6442b88e625d098ce7d2f
Source dataset
uspto-grants-1991_03
Patent number
US04997942

Linked notes

Loading…