Ethyl Acetate → Methyl 4-(4-amino-3-chlorophenoxy)-7-methoxy-6-quinolinecarboxylate

HRID 853417Notes

Reaction equation

HRID 853417 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[Cl:9].[H-].[Na+].Cl[C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([C:23]([O:25][CH3:26])=[O:24])[CH:21]=2)[N:16]=[CH:15][CH:14]=1.C(OCC)(=O)C>CS(C)=O.O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([C:23]([O:25][CH3:26])=[O:24])[CH:21]=3)[N:16]=[CH:15][CH:14]=2)=[CH:4][C:3]=1[Cl:9]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 871844-Amino-3-chlorophenolHCID 22646520Methyl 4-chloro-7-methoxyquinoline-6-carboxylate

Product 1

HCID 22936599Methyl 4-(4-amino-3-chlorophenoxy)-7-methoxy-6-quinolinecarboxylateYield 58.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

After dissolving 4-amino-3-chlorophenol (3.17 g, 22.05 mmol) in dimethylsulfoxide (50 ml), sodium hydride (882 mg, 22.05 mmol) was gradually added at room temperature and the mixture was stirred for 30 minutes. The 4-chloro-7-methoxy-6-methoxycarbonylquinoline (3.70 g, 14.7 mmol) described in WO0050405 was added, and the mixture was heated at 100° C. for 3 hours. After standing to cool to room temperature, the reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off, silica gel column chromatography (eluent—ethyl acetate) was performed, the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (3.092 g, 8.62 mmol, 57.4%) as light brown crystals.

Workup

  1. additionwas gradually added at room temperature
  2. additionwas added
  3. temperatureto cool to room temperature
  4. washthe organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off
  7. additionthe fraction containing the target substance
  8. concentrationwas concentrated
  9. additiondiluted with hexane
  10. filtrationthe crystals were filtered out and
  11. customblow-dried

Sources & evidence

ORD record
ord-fc0f4e77f76e49369ddd94c5a3101718
Source dataset
uspto-grants-2007_08
Patent number
US07253286B2

Reaction notes

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