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

HRID 387917

Reaction equation

HRID 387917 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[Cl:9].[H-].[Na+].[CH2:12]([O:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24](Cl)=[CH:25][CH:26]=[N:27]2)=[CH:22][C:21]=1[C:31]([O:33][CH3:34])=[O:32])[C:13]1[CH:18]=[CH:17][CH: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:24]2[C:23]3[C:28](=[CH:29][C:20]([O:19][CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[C:21]([C:31]([O:33][CH3:34])=[O:32])[CH:22]=3)[N:27]=[CH:26][CH:25]=2)=[CH:4][C:3]=1[Cl:9]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 871844-Amino-3-chlorophenolHCID 22936661Methyl 7-(benzyloxy)-4-chloro-6-quinolinecarboxylate

Product 1

HCID 22936786Methyl 4-(4-amino-3-chlorophenoxy)-7-(benzyloxy)-6-quinolinecarboxylateYield 73.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

After dissolving 4-amino-3-chlorophenol (2.22 g, 15.45 mmol) in dimethylsulfoxide (40 ml), sodium hydride (618 mg, 15.45 mmol) was gradually added at room temperature and the mixture was stirred for 30 minutes. Methyl 7-(benzyloxy)-4-chloro-6-quinolinecarboxylate (4.05 g, 12.36 mmol) was added, and the mixture was heated at 100° C. for 2 hours while stirring. Upon cooling to room temperature, the reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with water and saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off and subjected to silica gel column chromatography (eluent-ethyl acetate), 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 (3.938 g, 9.06 mmol, 73.3%) as light brown crystals.

Workup

  1. additionwas gradually added at room temperature
  2. stirringwhile stirring
  3. temperatureUpon cooling to room temperature
  4. washthe organic layer was washed with water and saturated saline
  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-0e772ea4922e494b805817c786c1627b
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Linked notes

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