Sodium Hydroxide → 5-Methoxy-2-methylquinoline

HRID 1051550Notes

Reaction equation

HRID 1051550 reaction equation
Cl.Cl[C:3]1[CH:4]=[CH:5][C:6]([O:14][CH3:15])=[C:7]2[C:12]=1[N:11]=[C:10]([CH3:13])[CH:9]=[CH:8]2.[OH-].[Na+]>[Pd].CO>[CH3:15][O:14][C:6]1[CH:5]=[CH:4][CH:3]=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([CH3:13])=[N:11]2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 754807178-Chloro-5-methoxy-2-methylquinoline hydrochloride

Product 1

HCID 113327475-Methoxy-2-methylquinolineYield 101.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A 1000-mL round-bottom flask was charged with 8-chloro-5-methoxy-2-methylquinoline hydrochloride (50.0 g, 204.8 mmol), methanol (300 mL), aqueous sodium hydroxide solution (3 M, 205 mL), and 10% palladium on active carbon (25 g). The system was purged with hydrogen gas, and the resulting mixture was stirred under a hydrogen atmosphere for 3 h at room temperature. The reaction mixture was filtered through a pad of Celite and concentrated under vacuum to remove most of methanol. The resulting solution was extracted with ethyl acetate (2×2000 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (gradient elution with 0-20% ethyl acetate/petroleum ether) to afford 5-methoxy-2-methylquinoline (36 g, 63%) as a yellow solid. MS (ES, m/z): 174 [M+H]+

Workup

  1. customThe system was purged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through a pad of Celite
  3. concentrationconcentrated under vacuum
  4. customto remove most of methanol
  5. extractionThe resulting solution was extracted with ethyl acetate (2×2000 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified via column chromatography on silica gel (gradient elution with 0-20% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-e28e38bcce4c4faa9872e6e8e9bd0336
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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