4-Aminophenol → 4-(3-(Pyridin-4-yl)pyridin-2-yloxy)benzenamine

HRID 473607Notes

Reaction equation

HRID 473607 reaction equation
F[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[N:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]([O:21][C:18]3[CH:19]=[CH:20][C:15]([NH2:14])=[CH:16][CH:17]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 463158192-Fluoro-3-(pyridin-4-yl)pyridine

Product 1

HCID 593271694-(3-(Pyridin-4-yl)pyridin-2-yloxy)benzenamine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a 50 mL round-bottomed flask was added 2-fluoro-3-(pyridin-4-yl)pyridine (1.0080 g, 5.787 mmol), 4-aminophenol (0.7102 g, 5.793 mmol), and cesium carbonate (2.387 g, 6.945 mmol) in dimethyl sulfoxide at 90° C. The reaction was monitored by LCMS to completion. The reaction mixture was diluted with water (10 mL) and extracted with DCM (3×10 mL). The organic extract was washed with water (3×10 mL), satd sodium chloride solution (3×10 mL), dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (40M), eluting with a gradient of 1% to 5% methanol in DCM, to provide 4-(3-(pyridin-4-yl)pyridin-2-yloxy)benzenamine.

Workup

  1. extractionextracted with DCM (3×10 mL)
  2. extractionThe organic extract
  3. washwas washed with water (3×10 mL), satd sodium chloride solution (3×10 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed through a Biotage™ pre-packed silica gel column (40M)
  8. washeluting with a gradient of 1% to 5% methanol in DCM

Sources & evidence

ORD record
ord-a54bf32ae46444d0b31e294c6dffcf93
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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