Methyl iodide → 7-Methoxy-3,4-dihydroquinolin-2(1H)-one

HRID 1183764Notes

Reaction equation

HRID 1183764 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.[C:13](=O)([O-])[O-].[K+].[K+].IC>C(O)(C)C>[CH3:13][O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 27857587-Hydroxy-3,4-dihydrocarbostyril

Product 1

HCID 128994187-Methoxy-3,4-dihydroquinolin-2(1H)-oneYield 90%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 7-hydroxy-3,4-dihydroquinolin-2(1H)-one (3) (16.317 g, 100 mmol) in anhydrous isopropanol (200 mL) was added potassium carbonate (16.585 g, 120.0 mmol) with stirring under an atmosphere of dry N2. The reaction mixture was stirred at room temperature for 30 minutes, then iodomethane (10.0 mL, 161.3 mmol) was added slowly. The reaction was heated to reflux with stirring for 60 hours, cooled, and the solvent evaporated under reduced pressure. To this residue water (200 mL) was added, and the mixture stirred and sonicated, filtered, and the pale yellow solid was washed with water (1000 mL), and dried under rescued pressure. To the crude dry solid was added 15% ethyl acetate in n-hexane (150 mL), and the mixture sonicated, filtered, washed with n-hexane (50 mL), and dried under reduced pressure, to afford 7-methoxy-3,4-dihydroquinolin-2(1H)-one (15.865 g, 89.5 mmol, 90%), the compound of formula (4). LCMS mz 178.0 (M+H), 200.0 (M+Na), anal HPLC>95% in purity, 1H NMR (400 MHz; dmso-D6) δ 7.09 (d, J=8.2 Hz, 1H); 6.57 (dd, J=8.2 and 2.7 Hz, 1H); 6.48 (d, J=2.7 Hz, 1H); 3.78 (s, 2H); 2.90 (t, J=7.0 Hz, 2H); 2.57 (t, J=7.0 Hz, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  2. temperatureThe reaction was heated
  3. temperatureto reflux
  4. stirringwith stirring for 60 hours
  5. temperaturecooled
  6. customthe solvent evaporated under reduced pressure
  7. additionTo this residue water (200 mL) was added
  8. stirringthe mixture stirred
  9. customsonicated
  10. filtrationfiltered
  11. washthe pale yellow solid was washed with water (1000 mL)
  12. customdried under rescued pressure
  13. customTo the crude dry solid
  14. additionwas added 15% ethyl acetate in n-hexane (150 mL)
  15. customthe mixture sonicated
  16. filtrationfiltered
  17. washwashed with n-hexane (50 mL)
  18. customdried under reduced pressure

Sources & evidence

ORD record
ord-bafc9d8bc55747fea1be373476474734
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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