4-Aminophenol → 4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)aniline

HRID 410211Notes

Reaction equation

HRID 410211 reaction equation
F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]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>[O:11]1[CH2:12][CH2:13][CH: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)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 593271552-Fluoro-3-(tetrahydro-2H-pyran-4-yl)pyridine

Product 1

HCID 593271274-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)aniline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a round bottomed flask was added 2-fluoro-3-(tetrahydro-2H-pyran-4-yl)pyridine (3.4590 g, 19.09 mmol), 4-aminophenol (3.12 g, 28.6 mmol), and cesium carbonate (18.66 g, 57.3 mmol) in DMSO (63.6 mL) at 110° C. to stir overnight. Reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with DCM. The organic extract was washed 50% sodium chloride solution, 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% MeOH in DCM, to provide 4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)aniline. MS (ESI, pos. ion) m/z: 271.1 (M+1).

Workup

  1. customReaction
  2. extractionextracted with DCM
  3. extractionThe organic extract
  4. washwas washed 50% sodium chloride solution
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed through a Biotage pre-packed silica gel column (40M)
  9. washeluting with a gradient of 1% to 5% MeOH in DCM

Sources & evidence

ORD record
ord-b7eea3b72d094818bb68ad3bf74ae093
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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