Potassium Carbonate → 4-Fluoro-3-(pyridin-3-yl)aniline

HRID 2183902Notes

Reaction equation

HRID 2183902 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[F:8].C(B(CC)[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)C.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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:8][C:7]1[CH:6]=[CH:5][C:4]([NH2:9])=[CH:3][C:2]=1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 6428513-(Diethylboryl)pyridineHCID 27792863-Bromo-4-fluoroaniline

Product 1

HCID 222853304-Fluoro-3-(pyridin-3-yl)anilineYield 46.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-4-fluorophenylamine (7.92 g, 41.7 mmol), diethyl(3-pyridyl)borane (6.74 g, 45.9 mmol), tetrakis(triphenylphosphine)palladium(0) (0.96 g, 0.83 mmol) and potassium carbonate (17.26 g, 125 mmol) in 1,2-dimethoxyethane (30 ml) and water (15 ml) was heated at 80° C. for 20 h. After cooling to ambient temperature the reaction was partitioned between ethyl acetate (500 ml) and water (500 ml). The organics were washed with brine (400 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel, eluting with dichloromethane on a gradient of ethyl acetate (0%-20%) gave 4-fluoro-3-(pyridin-3-yl)phenylamine (3.64 g, 46%) as a colourless oil that solidified on standing to afford a white solid: δH (360 MHz, CDCl3) 3.65 (2H, s), 6.65-6.72 (2H, m), 6.99 (1H, dd, J 9 and 9), 7.33-7.37 (1H, m), 7.84-7.86 (1H, m), 8.58 (1H, d, J 4), 8.76 (1H, m).

Workup

  1. temperatureAfter cooling to ambient temperature the reaction
  2. customwas partitioned between ethyl acetate (500 ml) and water (500 ml)
  3. washThe organics were washed with brine (400 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel
  8. washeluting with dichloromethane on a gradient of ethyl acetate (0%-20%)

Sources & evidence

ORD record
ord-8f313f3142db46b18fa4741b3d1d76c4
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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