4-Aminophenol → 4-(3-Morpholinopyridin-2-yloxy)benzenamine

HRID 410184Notes

Reaction equation

HRID 410184 reaction equation
F[C:2]1[C:7]([N: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:11]1[CH2:12][CH2:13][N: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

5

Reactant 3

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 585476984-(2-Fluoropyridin-3-yl)morpholine

Product 1

HCID 593272124-(3-Morpholinopyridin-2-yloxy)benzenamine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

To a 25 mL round-bottomed flask were added 4-(2-fluoropyridin-3-yl)morpholine (0.523 g, 2.87 mmol), 4-aminophenol (0.451 g, 2.88 mmol), cesium carbonate (1.18 g, 3.45 mmol) and DMSO (5 mL). The reaction mixture was heated at 120° C. for 8 h. After cooling to room temperature, the reaction mixture was filtered through SCX cartridges, and rinsed with DCM, MeOH, and 2.0 ammonia in MeOH. The ammonia rinses were combined 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 CH2Cl2, to provide 4-(3-morpholinopyridin-2-yloxy)benzenamine. MS: [M+1]=272.1

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction mixture was filtered through SCX cartridges
  3. washrinsed with DCM, MeOH, and 2.0 ammonia in MeOH
  4. concentrationconcentrated
  5. customchromatographed through a Biotage pre-packed silica gel column (40M)
  6. washeluting with a gradient of 1% to 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-3ad3bf63cf5f4127afdc176013080045
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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