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

HRID 410180Notes

Reaction equation

HRID 410180 reaction equation
F[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[CH3:14][C:10]1[CH:9]=[C:8]([C:7]2[C:2]([O:22][C:19]3[CH:20]=[CH:21][C:16]([NH2:15])=[CH:17][CH:18]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 3

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 585485722-Fluoro-3-(2-methylpyridin-4-yl)pyridine

Product 1

HCID 593271474-(3-(2-Methylpyridin-4-yl)pyridin-2-yloxy)benzenamine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a 25 mL round bottomed flask was added 2-fluoro-3-(2-methylpyridin-4-yl)pyridine (0.7204 g, 3.828 mmol), 4-aminophenol (0.4254 g, 3.832 mmol), and cesium carbonate (1.6144 g, 4.593 mmol) in dimethyl sulfoxide at 90° C. Upon completion, the reaction was filtered through Celite™ and the filtrate was condensed. The reaction mixture was diluted with water (50 mL) and extracted with DCM (3×20 mL). The organic extract was washed with water (3×15 mL), brine (3×15 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-(2-methylpyridin-4-yl)pyridin-2-yloxy)benzenamine.

Workup

  1. filtrationUpon completion, the reaction was filtered through Celite™
  2. customcondensed
  3. extractionextracted with DCM (3×20 mL)
  4. extractionThe organic extract
  5. washwas washed with water (3×15 mL), brine (3×15 mL)
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed through a Biotage™ pre-packed silica gel column (40M)
  10. washeluting with a gradient of 1% to 5% methanol in DCM

Sources & evidence

ORD record
ord-aa24c6733518428ba1630f19d68ee0e1
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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