Phosphorus oxychloride → Ethyl 4-chloro-7-methoxyquinoline-3-carboxylate

HRID 454185Notes

Reaction equation

HRID 454185 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12](=O)[C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][NH:15]2)=[CH:10][CH:9]=1>>[Cl:3][C:12]1[C:11]2[C:16](=[CH:17][C:8]([O:7][CH3:6])=[CH:9][CH:10]=2)[N:15]=[CH:14][C:13]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 296364Ethyl 4-hydroxy-7-methoxyquinoline-3-carboxylate

Product 1

HCID 728976Ethyl 4-chloro-7-methoxyquinoline-3-carboxylateYield 73%

Procedure

Phosphorus oxychloride (88 ml) was added to ethyl 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (58 g, 235 mmol) and the mixture was heated at reflux for 45 minutes under anhydrous conditions. Upon cooling to ambient temperature, phosphorus oxychloride was evaporated and the solid residue was added in portions to a mixture of ammonia (150 ml) and ice (200 g). External cooling as well as further addition of ammonia to maintain the pH around 8 was needed during this hydrolysis step. The aqueous phase was extracted with dichloromethane and the organic phase was washed with water and brine, dried (MgSO4) and concentrated to about 300 ml. Pentane (400 ml) was added and the precipitate formed collected by filtration. Drying under vacuum gave 4-chloro-3-ethoxycarbonyl-7-methoxyquinoline (45.5 g, 73%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 45 minutes under anhydrous conditions
  3. customphosphorus oxychloride was evaporated
  4. additionthe solid residue was added in portions to a mixture of ammonia (150 ml) and ice (200 g)
  5. temperatureExternal cooling as
  6. additionwell as further addition of ammonia
  7. temperatureto maintain the pH around 8
  8. customwas needed during this hydrolysis step
  9. extractionThe aqueous phase was extracted with dichloromethane
  10. washthe organic phase was washed with water and brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated to about 300 ml
  13. additionPentane (400 ml) was added
  14. customthe precipitate formed
  15. filtrationcollected by filtration
  16. customDrying under vacuum

Sources & evidence

ORD record
ord-963c570de0a54ca5b7441b7fbb3fb2f3
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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