Potassium Iodide → 8-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-one

HRID 525881Notes

Reaction equation

HRID 525881 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH3:12])[CH:9]=[C:8]([OH:13])[C:7]2=[O:14].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1.[I-].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH3:12])[CH:9]=[C:8]([O:13][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[C:7]2=[O:14]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 867327478-bromo-3-hydroxy-1-methylquinolin-4(1H)-one

Product 1

HCID 867327488-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-oneYield 77.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 8-bromo-3-hydroxy-1-methylquinolin-4(1H)-one (2.4 g, 8.97 mmol) and potassium carbonate (1.488 g, 10.77 mmol) in N,N-dimethylformamide (50 mL) was heated at 90° C. for 0.5 h. Then 1-(chloromethyl)-4-methoxybenzene (1.442 mL, 9.87 mmol) and potassium iodide (0.149 g, 0.897 mmol) were added, and the mixture was heated at the same temperature for another 2 h. After cooling. N,N-dimethylformamide was removed in vacuo and the residue was partitioned between dichloromethane and brine. The organic phase was separated, the aqueous phase was extracted with dichloromethane for several times. The combined organic extracts were dried over sodium sulfate, filtered and concentrated, The residue was purified by automatic silica gel column chromatography (Combiflash RF), eluting with ethyl acetate/hexanes (0-100%) to afford 8-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-one (2.6 g, 6.95 mmol, 77% yield) as a light brown solid. LCMS: (M+H)+: 374.0.

Workup

  1. temperaturethe mixture was heated at the same temperature for another 2 h
  2. temperatureAfter cooling
  3. customN,N-dimethylformamide was removed in vacuo
  4. customthe residue was partitioned between dichloromethane and brine
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with dichloromethane for several times
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by automatic silica gel column chromatography (Combiflash RF)
  11. washeluting with ethyl acetate/hexanes (0-100%)

Sources & evidence

ORD record
ord-3102c36839044c9691a67bbac0b8599e
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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