Water → 5-Amino-2-fluoro-4-methylbenzonitrile

HRID 1773080Notes

Reaction equation

HRID 1773080 reaction equation
Br[C:2]1[C:3]([F:10])=[CH:4][C:5]([CH3:9])=[C:6]([CH:8]=1)[NH2:7].[Cu][C:12]#[N:13].O.[OH-].[NH4+]>CN1CCCC1=O>[NH2:7][C:6]1[C:5]([CH3:9])=[CH:4][C:3]([F:10])=[C:2]([CH:8]=1)[C:12]#[N:13]

Participants

6

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 27827865-Bromo-4-fluoro-2-methylanilineHCID 178418546HCID 178418546, compound

Product 1

HCID 866774495-Amino-2-fluoro-4-methylbenzonitrileYield 68.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

The starting 5-bromo-4-fluoro-2-methylaniline (1) (20 g, 98 mmol) was dissolved in anhydrous 1-methylpyrrolidinone (100 mL), and copper (I) cyanide (17.6 g, 196 mmol) was added. The reaction was heated to 180° C. for 3 hours, cooled to room temperature, and water (300 mL) and concentrated ammonium hydroxide (300 mL) added. The mixture was stirred for 30 minutes and extracted with EA (3×200 mL). The combined extracts were dried over magnesium sulfate, and the solvent was removed under reduced pressure. The oily residue was washed with hexanes (2×100 mL), and the solid dissolved in dichloromethane and loaded onto a silica gel column. Eluting with 0 to 25% EA in hexanes gradient provided 5-amino-2-fluoro-4-methylbenzonitrile (10.06 g, 67.1 mmol). LC/MS (m/z:151 M+1).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EA (3×200 mL)
  3. dry with materialThe combined extracts were dried over magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. washThe oily residue was washed with hexanes (2×100 mL)
  6. dissolutionthe solid dissolved in dichloromethane
  7. washEluting with 0 to 25% EA in hexanes gradient

Sources & evidence

ORD record
ord-2bb63b6f191e4b8bab4f9a89ef9be5a6
Source dataset
uspto-grants-2016_02
Patent number
US09254284B2

Reaction notes

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