4-Aminophenol → 4-(Pyridin-2-yloxy)aniline

HRID 1956426Notes

Reaction equation

HRID 1956426 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[H][H].Br[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1>CN(C=O)C>[N:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 79732-BromopyridineHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 131505744-(Pyridin-2-yloxy)aniline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Aminophenol (27.3 g) in DMF (200 ml) was added dropwise over 30 minutes to a stirred suspension of sodium hydride (10.0 g, 60% dispersion in mineral oil) in DMF (200 ml) with stirring under nitrogen. When the evolution of hydrogen had ceased, 2-bromopyridine (39.5 g) was added and the resultant solution was heated at 120° C. for 6 hours. The DMF was removed under reduced pressure, the residue was dissolved in water (250 ml) and the mixture extracted with dichloromethane. The combined organic extracts were washed with water, 1M sodium hydroxide solution and then again with water and then with 2M hydrochloric acid. The acid extracts were basified and extracted with dichloromethane to give an oil which solidified on standing. This solid was triturated in petroleum ether, b.p. 40°-60° C./ethyl acetate (10:1) to give 4-(2-pyridyloxy)aniline, m.p. 64°-67° C.

Workup

  1. customThe DMF was removed under reduced pressure
  2. dissolutionthe residue was dissolved in water (250 ml)
  3. extractionthe mixture extracted with dichloromethane
  4. washThe combined organic extracts were washed with water, 1M sodium hydroxide solution
  5. extractionextracted with dichloromethane
  6. customto give an oil which
  7. customThis solid was triturated in petroleum ether

Sources & evidence

ORD record
ord-a45ad63bcb6a450aaea72cb4dc6d02ff
Source dataset
uspto-grants-1998_07
Patent number
US05780482

Reaction notes

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