Sodium hydride → 5-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-one

HRID 901866Notes

Reaction equation

HRID 901866 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][N:5]([CH3:13])[C:6](=[O:12])[NH:7]2.[H-].[Na+].[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20]Br>CN(C)C=O>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][N:5]([CH3:13])[C:6](=[O:12])[N:7]2[CH2:20][C:19]1[CH:22]=[CH:23][CH:24]=[C:17]([F:16])[CH:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680073-Fluorobenzyl bromideHCID 184445245-Bromo-3,4-dihydro-3-methylquinazolin-2(1H)-one

Product 1

HCID 184445195-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-oneYield 81.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one (132 mg, 0.55 mmol) in 5 ml anhydrous dimethylformamide was added sodium hydride (33 mg of a 60% suspension in mineral oil, 0.83 mmol) portionwise at 0° C. The solution was stirred with a magnetic stirrer at 0° C. for 20 minutes, at which time the initial offgassing ended. 3-Fluorobenzyl bromide (0.08 ml, 0.65 mmol) was added in one portion and the reaction mixture was stirred at 0° C. for an hour. The solution was allowed to warm to room temperature and the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting residue was purified by flash chromatography to give 156 mg of 5-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-one as a yellow solid (81%). MS: 349.1 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for an hour
  2. temperatureto warm to room temperature
  3. customthe reaction mixture was partitioned between water and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic fractions were washed with water and brine
  6. dry with materialAfter drying over MgSO4
  7. concentrationthe organic fraction was concentrated in vacuo
  8. customresulting residue
  9. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-b93d93e118ad4d0e8e2a8b500e979668
Source dataset
uspto-grants-2008_04
Patent number
US07365063B2

Reaction notes

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