Water → 2-Amino-5-bromo-4-fluoro-3-methoxy-6-methylbenzonitrile

HRID 17302Notes

Reaction equation

HRID 17302 reaction equation
O.C[N:3]([CH3:6])C=O.[Br:7][C:8]1[C:13]([CH3:14])=[C:12](I)[C:11]([NH2:16])=[C:10]([O:17][CH3:18])[C:9]=1[F:19]>[Cl-].[Na+].O.[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[NH2:16][C:11]1[C:10]([O:17][CH3:18])=[C:9]([F:19])[C:8]([Br:7])=[C:13]([CH3:14])[C:12]=1[C:6]#[N:3]

Participants

8

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 860974524-Bromo-3-fluoro-6-iodo-2-methoxy-5-methylphenylamine

Product 1

HCID 860974532-Amino-5-bromo-4-fluoro-3-methoxy-6-methylbenzonitrileYield 80%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
125 °C

Procedure

Under nitrogen atmosphere, water (0.1 ml), zinc cyanide (59 mg, 0.5 mmol), 1,1′-bis(diphenylphosphino)ferrocene (67 mg, 0.12 mmol), bis(dibenzylideneacetone)palladium(0) (58 mg, 0.1 mmol) were added to an N,N-dimethylformamide (10 ml) solution of 4-bromo-3-fluoro-6-iodo-2-methoxy-5-methylphenylamine (I-44) (359 mg, 1.0 mmol), followed by stirring at 120 to 130° C. for 3 hours. After cooling to room temperature, saturated brine was added to the reaction liquid, followed by extraction twice with ethyl acetate, the organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with n-hexane:ethyl acetate (10:1) was concentrated under reduced pressure to obtain the entitled compound (208 mg, 80%) as a white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction twice with ethyl acetate
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. concentrationthe eluate with n-hexane:ethyl acetate (10:1) was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b67f5b654e26443085e2cac454960056
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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