Potassium Carbonate → 2,4-Difluoro-3-(pyridin-3-yl)aniline

HRID 891860Notes

Reaction equation

HRID 891860 reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[F:8].C(B(CC)[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:10][C:3]1[C:2]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[C:7]([F:8])[CH:6]=[CH:5][C:4]=1[NH2:9]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 6428513-(Diethylboryl)pyridineHCID 137327463-Bromo-2,4-difluoroaniline

Product 1

HCID 137730352,4-Difluoro-3-(pyridin-3-yl)anilineYield 47%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-bromo-2,4-difluorophenylamine (from Example 2, step b) (12.5 g, 60 mmol), diethyl(3-pyridyl)borane (10.6 g, 72 mmol) and potassium carbonate (16.6 g, 120 mmol) in tetrahydrofuran (150 ml) and water (50 ml) was degassed with nitrogen for 15 min. To this mixture was added tetrakis(triphenylphosphine)palladium(0) (2.1 g, 1.8 mmol) and the reaction was heated at reflux for 4 days. The mixture was cooled to ambient temperature and the majority of the tetrahydrofuran removed on a rotary evaporator. The residue was diluted with water (250 ml), extracted with ethyl acetate (300 ml), the organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography [silica gel, 10–50% EtOAc/isohexane (containing 1% triethylamine)] afforded 5.8 g (47%) of the title compound as a cream-coloured solid: 1H NMR (400 MHz, CDCl3) δ 3.69 (2H, br s), 6.72–6.88 (2H, m), 7.39 (1H, dd, J 8, 5), 7.80 (1H, d, J 8), 8.62 (1H, dd, J 5, 1), 8.72 (1H, s).

Workup

  1. customwas degassed with nitrogen for 15 min
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 4 days
  4. customthe majority of the tetrahydrofuran removed on a rotary evaporator
  5. additionThe residue was diluted with water (250 ml)
  6. extractionextracted with ethyl acetate (300 ml)
  7. washthe organics were washed with water, brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered and pre-adsorbed onto silica
  10. customPurification by chromatography [silica gel, 10–50% EtOAc/isohexane (containing 1% triethylamine)]

Sources & evidence

ORD record
ord-36cb592d87854d4f9b1f14f1281270d3
Source dataset
uspto-grants-2006_02
Patent number
US07005431B2

Reaction notes

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