Potassium Carbonate → Ethyl 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 525960Notes

Reaction equation

HRID 525960 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([OH:14])[C:9]([OH:13])=[CH:10][CH:11]=2)[C:6](=[O:15])[C:5]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:4]1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH3:27][O:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Cl)=[CH:31][CH:30]=1>CC(C)=O>[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([OH:14])[C:9]([O:13][CH2:33][C:32]3[CH:35]=[CH:36][C:29]([O:28][CH3:27])=[CH:30][CH:31]=3)=[CH:10][CH:11]=2)[C:6](=[O:15])[C:5]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 86732826Ethyl 1-ethyl-5,6-dihydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 86732827Ethyl 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 20.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of ethyl 1-ethyl-5,6-dihydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (5 g, 18.03 mmol) and potassium carbonate (8.72 g, 63.1 mmol) in Acetone (120 mL) at r.t. was added 4-methoxybenzyl chloride (7.37 mL, 54.1 mmol) and KI (0.599 g, 3.61 mmol). The mixture was heated under reflux for 2 days. After cooling, the reaction mixture was filtered and the filtrate was concentrated. The residue was partitioned between DCM and water, and the organic layer was washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. The crude product was purified by normal phase automatic silica column chromatography (Combiflash RF), eluting with EtOAc/hexanes (0-100%) to afford ethyl 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylate (1.5 g, 3.77 mmol, 20.9% yield) as a light yellow solid that contained some PMB-ester. LCMS: (M+H)+: 398.3.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2 days
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was partitioned between DCM and water
  7. washthe organic layer was washed with sat. NaHCO3 and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude product was purified by normal phase automatic silica column chromatography (Combiflash RF)
  11. washeluting with EtOAc/hexanes (0-100%)

Sources & evidence

ORD record
ord-722a1d4a43c844538bb2080073750705
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

Loading…