3-Hydroxypyridine → 3-(3-Nitrophenoxy)pyridine

HRID 1696433Notes

Reaction equation

HRID 1696433 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].F[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1.[NH4+].[Cl-]>CS(C)=O>[N+:17]([C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)[O:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)([O-:19])=[O:18]

Participants

6

Reactant 4

HCID 79713-HydroxypyridineHCID 98231-Fluoro-3-nitrobenzeneHCID 24758Sodium hydrideHCID 25517Ammonium Chloride

Product 1

HCID 212855723-(3-Nitrophenoxy)pyridineYield 39%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 3-hydroxypyridine (5.01 g, 52.7 mmol) in DMSO (60 mL) was added NaH (1.39 g, 57.9 mmol, 2.31 g of 60% suspended in oil) and stirred for 30 min at RT. To the slurry was added 1-fluoro-3-nitrobenzene (9.66 g, 68.5 mmol) and mixture was heated to 80° C. for 72 h. The mixture was poured into satd NH4Cl solution (200 mL), and extracted with EtOAc (3×125 mL). The combined organic extracts were washed with H2O (75 mL), brine, dried (Na2SO4) and concentrated to yield a crude residue which was purified by column chromatography afford (4.43 g, 39% yield) pure 3-(3-nitrophenoxy)pyridine as a syrup. 1H NMR (400 MHz, Acetone-d6): δ 8.49-8.47 (m, 2H), 8.07-8.05 (m, 1H), 7.85 (t, J=2.4 Hz, 1H), 7.74 (t, J=8.4 Hz, 1H), 7.58-7.53 (m, 2H), 7.51-7.47 (m, 1H); MS (ESI) m/z: 217.0 (M+H+).

Workup

  1. temperaturewas heated to 80° C. for 72 h
  2. extractionextracted with EtOAc (3×125 mL)
  3. washThe combined organic extracts were washed with H2O (75 mL), brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto yield a crude residue which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-48fcd7d1d83a4576904c00a78e68144d
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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