Sodium hydride → 4-(Pyridin-2-ylmethoxy)pyridine 1-oxide

HRID 2387512Notes

Reaction equation

HRID 2387512 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([OH:14])C1C=CC=CC=1.[H-].[Na+].Cl[C:18]1[CH:23]=[CH:22][N+:21]([O-:24])=[CH:20][CH:19]=1>O1CCOCC1>[CH3:7][OH:14].[NH3:1].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:14][C:18]1[CH:23]=[CH:22][N+:21]([O-:24])=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 707244-chloropyridine N-oxideHCID 315585Phenyl(pyridin-2-yl)methanol

Product 2

HCID 21705897Ammonia methanolHCID 684584404-(Pyridin-2-ylmethoxy)pyridine 1-oxideYield 38.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

2-Pyridylbenzylalcohol (1.67 g, 15.3 mmol) was dissolved in 1,4-dioxane (25 mL) and NaH (0.92 g, 23 mmol) was added. After stirring for 30 minutes, 4-chloropyridine-N-oxide (2.27 g, 17.5 mmol) was added and the reaction mixture was heated for 1 h at 120° C. Upon cooling, the mixture was purified by column chromatography (40 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1), gradient 100% methylene chloride to 90% methylene chloride over 30 min at 40 mL/min) to provide the title compound (600 mg, 38%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 8.62-8.61 (m, 1H), 8.13-8.10 (m, 2H), 7.74-7.73 (dt, J=7.8, 1.4 Hz, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.30-7.29 (d, J=4.8 Hz, 1H), 6.92-6.89 (m, 2H), 5.23 (s, 2H).

Workup

  1. temperatureUpon cooling
  2. customthe mixture was purified by column chromatography (40 g ISCO column
  3. washeluting with methylene chloride

Sources & evidence

ORD record
ord-4ae3ead4a0b64b06aaa43dfaddecff17
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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