Hydrochloric Acid → Ethyl 2-methyl-4-(3-phenyl-quinolin-5-yl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carboxylate

HRID 1590872Notes

Reaction equation

HRID 1590872 reaction equation
[C:1]1([C:7]2[CH:8]=[N:9][C:10]3[CH:11]=[CH:12][CH:13]=[C:14]([CH:17]=O)[C:15]=3[CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].[NH2:25]/[C:26](/[CH2:33]OC(=O)C)=[CH:27]\[C:28]([O:30][CH2:31][CH3:32])=[O:29].[OH-].[K+].Cl>C(O)C.CO>[CH3:33][C:26]1[NH:25][C:24]2[CH2:23][O:22][C:19](=[O:21])[C:20]=2[CH:17]([C:14]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:15]=2[CH:16]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]=[N:9]3)[C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 151703323-Phenylquinoline-5-carbaldehydeHCID 57476884Ethyl 3-amino-4-acetoxycrotonate

Product 1

HCID 15170335Ethyl 2-methyl-4-(3-phenyl-quinolin-5-yl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carboxylateYield 18%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

1.4 g (6.0 mmol) of 3-phenylquinoline-5-aldehyde in 20 ml of ethanol are boiled with 0.79 ml (6.2 mmol) of ethyl acetate and 1.16 g (6.2 mmol) of ethyl 3-amino-4-acetoxycrotonate for 2 days. The mixture is cooled and concentrated. The residue is coarsely purified by flash chromatography. The intermediate obtained is boiled in a solution of 970 mg of potassium hydroxide in 50 ml of methanol for 40 minutes. The mixture is cooled, adjusted to pH 5 with 10% strength hydrochloric acid and concentrated, the residue is taken up in ethyl acetate and the solution is washed with water. The organic phase is dried and concentrated. The residue is freed from by-products by column chromatography, and the fractions are concentrated and crystallized from acetonitrile. 460 mg of colorless crystals of melting point 257-260° C. are obtained.

Workup

  1. temperatureThe mixture is cooled
  2. concentrationconcentrated
  3. customThe residue is coarsely purified by flash chromatography
  4. customThe intermediate obtained
  5. temperatureThe mixture is cooled
  6. concentrationconcentrated
  7. washthe solution is washed with water
  8. customThe organic phase is dried
  9. concentrationconcentrated
  10. concentrationthe fractions are concentrated
  11. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-8d6fdf7b33014c368f202ff108cb051d
Source dataset
uspto-grants-1993_04
Patent number
US05204472

Reaction notes

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