Pyridine → 3-(Pyridin-3-yloxy)benzonitrile

HRID 2401493Notes

Reaction equation

HRID 2401493 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[OH:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.C([O-])([O-])=O.[K+].[K+].N1C=CC=CC=1>[O-2].[Cu+2].C(Cl)Cl>[N:13]1[CH:14]=[CH:15][CH:16]=[C:11]([O:10][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[C:5]#[N:6])[CH:12]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 79713-HydroxypyridineHCID 11430Potassium CarbonateHCID 233813-Bromobenzonitrile

Product 1

HCID 578393623-(Pyridin-3-yloxy)benzonitrileYield 76.5%

Reagents, catalysts & solvents 2

HCID 164827Copper oxide (CuO)CatalystHCID 6344DichloromethaneSolvent

Procedure

Cu(II) oxide (2.1 g, 26 mmol, 2.5 eq) was added to a mixture of 3-bromobenzonitrile (3.8 g, 21 mmol, 2.0 eq), 3-hydroxypyridine (1.0 g, 10 mmol, 1.0 eq), K2CO3 (3.0 g, 22 mmol, 2.1 eq) and pyridine (35 mL) at 80° C. The mixture was refluxed vigorously for 20 h and cooled to rt. CH2Cl2 was added and the mixture was filtered through celite. Pyridine was removed in vacuo and the residue dissolved in EtOAc and washed with 1N HCl (1×), 1N NaOH (1×), brine (1×), dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 1.5 g (73%) of the title compound as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 8.15 (dd, J=4.9, 1.6 Hz, 1H), 7.89 (td, J=7.6, 2.0 Hz, 1H), 7.69-7.67 (m, 2H), 7.61 (t, J=8.0 Hz, 1H), 7.51-7.49 (m, 1H), 7.17 (dd, J=7.0, 5.1 Hz, 1H), 7.12 (d, J=8.3 Hz, 1H); ES-MS [M+1]+: 197.2.

Workup

  1. temperatureThe mixture was refluxed vigorously for 20 h
  2. filtrationthe mixture was filtered through celite
  3. customPyridine was removed in vacuo
  4. dissolutionthe residue dissolved in EtOAc
  5. washwashed with 1N HCl (1×), 1N NaOH (1×), brine (1×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-d9e7aca06b82472db974ec17d79f9c99
Source dataset
uspto-grants-2014_08
Patent number
US08796295B2

Reaction notes

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