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

HRID 2191998Notes

Reaction equation

HRID 2191998 reaction equation
F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N: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][N:6]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 593512282-fluoro-3-(Tetrahydro-2H-pyran-4-yl)pyrazine

Product 1

HCID 593511704-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

To a round bottomed flask was added 2-fluoro-3-(tetrahydro-2H-pyran-4-yl)pyrazine (1.1147 g, 6.12 mmol), 4-aminophenol (0.801 g, 7.34 mmol), and cesium carbonate (5.98 g, 18.35 mmol) in DMSO (20.39 mL) in DMSO at 110° C. to stir overnight. The reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with DCM. The organic extract was washed with 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)pyrazin-2-yloxy)aniline. [M+H]=272.1.

Workup

  1. extractionextracted with DCM
  2. extractionThe organic extract
  3. washwas washed with 50% sodium chloride solution
  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% MeOH in DCM

Sources & evidence

ORD record
ord-bef52c733a9d404f9722a9af563382d2
Source dataset
uspto-grants-2012_12
Patent number
US08329700B2

Reaction notes

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