Sodium Hydroxide → 3-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carboxamide

HRID 525883Notes

Reaction equation

HRID 525883 reaction equation
[CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]([CH2:7][O:8][C:9]2[C:18](=[O:19])[C:17]3[C:12](=[C:13]([C:20]#[N:21])[CH:14]=[CH:15][CH:16]=3)[N:11]([CH3:22])[CH:10]=2)=[CH:5][CH:4]=1.[OH-:25].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[C:18](=[O:19])[C:17]3[C:12](=[C:13]([C:20]([NH2:21])=[O:25])[CH:14]=[CH:15][CH:16]=3)[N:11]([CH3:22])[CH:10]=2)=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 867327493-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carbonitrile

Product 1

HCID 867327503-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carboxamideYield 65.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinoline-8-carbonitrile (1.75 g, 5.46 mmol) and 25% aqueous sodium hydroxide (20 mL) in methanol (100 mL) was stirred at reflux for 3 h. After complete consumption of the nitrile, the mixture was concentrated to remove ˜75% of the methanol. The mixture was acidified to pH 3 with 1 M HCl (aq), and partitioned between EtOAc and brine. The organic phase was separated, dried over sodium sulfate and concentrated in vacuo. The crude product was absorbed onto silica gel and purified by automatic silica gel column chromatography (Combiflash RF), eluting with methanol/dichloromethane (0-30%) to afford 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinoline-8-carboxamide (1.21 g, 3.58 mmol, 65.5% yield) as light brown solid. LCMS (M+H)+: 339.3.

Workup

  1. temperatureat reflux for 3 h
  2. customAfter complete consumption of the nitrile
  3. concentrationthe mixture was concentrated
  4. customto remove ˜75% of the methanol
  5. custompartitioned between EtOAc and brine
  6. customThe organic phase was separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude product was absorbed onto silica gel
  10. custompurified by automatic silica gel column chromatography (Combiflash RF)
  11. washeluting with methanol/dichloromethane (0-30%)

Sources & evidence

ORD record
ord-caf057919fd14d369c2c4ea4acfa3d76
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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