Sodium hydride → 5-Bromo-1-(4-methoxybenzyl)quinolin-2(1H)-one

HRID 2175212Notes

Reaction equation

HRID 2175212 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:12])[NH:7]2.[H-].[Na+].[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1>CN(C=O)C>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:12])[N:7]2[CH2:21][C:20]1[CH:23]=[CH:24][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 142210325-Bromo-1,2-dihydroquinolin-2-one

Product 1

HCID 709830295-Bromo-1-(4-methoxybenzyl)quinolin-2(1H)-oneYield 106.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromoquinolin-2(1H)-one (0.84 g, 2.29 mmol) in DMF (20 mL) at room temperature was added sodium hydride (0.57 g, 14.22 mmol) and 4-methoxybenzyl chloride (1.24 mL, 9.10 mmol). Upon completion of addition, the reaction mixture was stirred at room temperature for 2 d, and then heat to 75° C. where it stirred for 2 h. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by flash chromatography (0 to 30% ethyl acetate:hexanes) to afford the title compound (0.84 g, 40% yield) as a white powder. LCMS, [M+H]+=344.0. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=9.8 Hz, 1H), 7.44 (dd, J=6.6, 2.2 Hz, 1H), 7.28-7.23 (m, 3H), 7.14 (d, J=8.2 Hz, 1H), 6.89 (d, J=9.8 Hz, 1H), 6.83 (d, J=8.6 Hz, 2H), 5.5 (s, 2H), 3.76 (s, 3H).

Workup

  1. additionUpon completion of addition
  2. temperatureheat to 75° C. where it
  3. stirringstirred for 2 h
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was quenched with water
  6. extractionextracted with EtOAc
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue was purified by flash chromatography (0 to 30% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-fc11ff64666f495b98792ce31d0a712f
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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