4-Bromo-2,6-difluoroaniline → 4-Amino-3,5-difluorobenzonitrile

HRID 2105059Notes

Reaction equation

HRID 2105059 reaction equation
[C:1]([Cu])#[N:2].Br[C:5]1[CH:10]=[C:9]([F:11])[C:8]([NH2:12])=[C:7]([F:13])[CH:6]=1>CN(C=O)C>[NH2:12][C:8]1[C:9]([F:11])=[CH:10][C:5]([C:1]#[N:2])=[CH:6][C:7]=1[F:13]

Participants

4

Reactant 2

HCID 6101914-Bromo-2,6-difluoroanilineHCID 178418546HCID 178418546, compound

Product 1

HCID 2804674-Amino-3,5-difluorobenzonitrileYield 78.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
220 °C

Procedure

A solution of CuCN (135 mg, 1.51 mmol) and 4-bromo-2,6-difluorobenzenamine (200 mg, 0.96 mmol) in DMF (4 mL) was sealed in a microwave vial and degassed with Ar. The mixture was heated in microwave at 220° C. for 17.5 min. Ammonium hydroxide (10 mL) and water (10 mL) were added to the mixture and it was extracted with EtOAc (2×20 mL). The organics were combined, washed with sat. NaHCO3 and brine, dried (Na2SO4) and concentrated. Purification by flash chromatography yielded 116 mg of Intermediate 383.1 as a white solid. LCMS 155.3 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 4.27 (bs, 2H) 7.12 (dd, J=5.87, 2.20 Hz, 2H).

Workup

  1. customdegassed with Ar
  2. additionAmmonium hydroxide (10 mL) and water (10 mL) were added to the mixture and it
  3. extractionwas extracted with EtOAc (2×20 mL)
  4. washwashed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-4acb2e5acdb74b728bf19f6ad587ac40
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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