Sodium hydride → 1-(4-Benzyloxybenzyl)-6-bromo-1H-pyridin-2-one

HRID 1950017Notes

Reaction equation

HRID 1950017 reaction equation
[Br:1][C:2]1[NH:7][C:6](=[O:8])[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br-].[Li+].[CH2:13]([O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>COCCOC.CN(C)C=O.O>[CH2:13]([O:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:25][N:7]2[C:2]([Br:1])=[CH:3][CH:4]=[CH:5][C:6]2=[O:8])=[CH:27][CH:28]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 700424-Benzyloxybenzyl chlorideHCID 82050Lithium BromideHCID 8204976-Bromo-2-hydroxypyridine

Product 1

HCID 230872391-(4-Benzyloxybenzyl)-6-bromo-1H-pyridin-2-oneYield 56.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

By referring to the synthetic method of Synthesis, 1974, 707, to a solution of 2,6-dibromopyridine (5.0 g) in tert-butanol (100 ml) was added potassium tert-butoxide (25 g), the solution was stirred overnight at 100° C., then ice was added to the reaction mixture, which was brought to pH 1 with 5N hydrochloric acid, then the solution was stirred overnight at room temperature. The solution was extracted with chloroform, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo to provide 6-bromo-1H-pyridin-2-one (2.5 g). By referring to the synthetic method of Tetrahedron Lett., 1995, 36, 8917, to a solution of 6-bromo-1H-pyridin-2-one (1.9 g) in 1,2-dimethoxyethane (27 ml) and N,N-dimethylformamide (3 ml) was added 60% sodium hydride (470 mg) on an ice bath under a nitrogen atmosphere, the solution was stirred for 15 minutes, then lithium bromide (3.85 g) was added thereto followed by stirring for 25 minutes at room temperature, 4-benzyloxybenzyl chloride (5.4 g) was added thereto followed by stirring overnight at 70° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (2.3 g).

Workup

  1. stirringby stirring for 25 minutes at room temperature
  2. stirringby stirring overnight at 70° C
  3. stirringby stirring
  4. extractionthe solution was extracted with ethyl acetate
  5. washsequentially washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate system)

Sources & evidence

ORD record
ord-e4dd65eb1b1d4f3381bc8471bd3996e1
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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