4-Aminophenol → 4-(Pyridin-4-yloxy)aniline

HRID 1993502Notes

Reaction equation

HRID 1993502 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl.Cl[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1.CC([O-])(C)C.[K+].O>CN1C(=O)N(C)CCC1.CN(C=O)C>[N:14]1[CH:15]=[CH:16][C:11]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 4034-AminophenolHCID 962WaterHCID 818524-Chloropyridine hydrochlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 115645894-(Pyridin-4-yloxy)aniline

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

A solution of 4-aminophenol (15 g, 0.135 mol), 4-chloropyridine hydrochloride (22.5 g, 0.148 mol), and KOtBu (45.8 g, 0.404 mol) in DMPU (208 ml) and DMF (52 ml) is stirred at 100° C. for 24 h, cooled to rt, poured into H2O (0.6 L), and extracted with AcOEt (150 ml, 6×). The combined organic phases are washed with H2O (100 ml, 2×), brine (100 ml, 2×), dried (Na2SO4), concentrated under reduced pressure, and flash chromatographed (silica gel, 4.5×25 cm; AcOEt/hexane=1:9→3:7) to give the title compound of Stage 1.1 as a colorless solid: M+H=187.2; 1H-NMR (400 MHz, DMSO-d6): 8.37 (d, 6.5 Hz, 2H, pyridinyl), 6.79 (d, 9.5 Hz, 2H, phenyl), 6.78 (d, 9.5 Hz, 2H, pyridinyl) 5.12 (s, 2H, NH2); Rf (AcOEt/CH2Cl2=3:7): 0.23; m.p.=165.8-166.6° C.

Workup

  1. extractionextracted with AcOEt (150 ml, 6×)
  2. washThe combined organic phases are washed with H2O (100 ml, 2×), brine (100 ml, 2×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure, and flash
  5. customchromatographed (silica gel, 4.5×25 cm; AcOEt/hexane=1:9→3:7)

Sources & evidence

ORD record
ord-f36f06932b8942009c79382a163ee6f0
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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