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Morpholine → 6-Chloro-2-morpholin-4-yl-4-phenyl-quinoline-3-carboxylic acid ethyl ester

HRID 1497057
Notes
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Reaction equation

HRID 1497057 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Cl:22])=[CH:11][CH:10]=2)=[O:5])[CH3:2].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[N:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Cl:22])=[CH:11][CH:10]=2)=[O:5])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 8083MorpholineHCID 1714247Ethyl 2,6-dichloro-4-phenylquinoline-3-carboxylate

Product 1

HCID 866829316-Chloro-2-morpholin-4-yl-4-phenyl-quinoline-3-carboxylic acid ethyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 2,6-dichloro-4-phenyl-quinoline-3-carboxylic acid ethyl ester (prepared as described in example 11 step B, 100 mg, 0.29 mmol) in a sealed tube was added morpholine (0.038 ml, 0.43 mmol). Then the mixture was stirred at 150° C. for 3 h. After cooling, this reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to afford a crude residue which was purified by flash column chromatography (100-200 mesh silica, eluting with 10% ethyl acetate in hexane) to give 6-chloro-2-morpholin-4-yl-4-phenyl-quinoline-3-carboxylic acid ethyl ester (65 mg, 57%) as pale yellow solid. LC-MS: 397 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford a crude residue which
  7. customwas purified by flash column chromatography (100-200 mesh silica, eluting with 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-61d0afad1fcc42329a8658502939fb12
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09199938B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes