4-Chloro-6,7-dimethoxyquinoline → {2-[(6,7-Dimethoxy-4-quinolyl)oxy]-4,5-dimethylphenyl}-(phenyl)methanone hydrochloride

HRID 228598Notes

Reaction equation

[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:10])=[C:4]([OH:17])[CH:3]=1.[Cl:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][CH:20]=1>ClC1C=CC=CC=1Cl>[ClH:18].[CH3:30][O:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[O:31][CH3:32])[N:22]=[CH:21][CH:20]=[C:19]2[O:17][C:4]1[CH:3]=[C:2]([CH3:1])[C:7]([CH3:8])=[CH:6][C:5]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10]

Participants

Conditions

Temperature: 180 °C

Procedure

(4,5-Dimethyl-2-methoxyphenyl)(phenyl)methanone (650 mg) was dissolved in dimethylformamide (10 ml) to prepare a solution. Sodium thiomethoxide (379 mg) was added to the solution, and the mixture was stirred while heating under reflux overnight. The reaction solution was cooled to room temperature, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate and was concentrated. The residue was subjected to separation and purification by column chromatography on silica gel using hexane/ethyl acetate as a solvent to give (4,5-dimethyl-2-hydroxy-phenyl)(phenyl)methanone. The (4,5-dimethyl-2-hydroxy-phenyl)(phenyl)methanone (40 mg) thus obtained and 4-chloro-6,7-dimethoxyquinoline (150 mg) were added to o-dichlorobenzene (0.2 ml), and the mixture was heated at 180° C. for two days. The reaction solution was concentrated and was subjected to separation and purification by column chromatography on silica gel using hexane-ethyl acetate. Subsequently, a hydrochloric acid-methanol mixed solution was added thereto, the solvent was removed by distillation, and the residue was suspended in ethyl acetate. The solid thus obtained was collected by filtration, was washed with ethyl acetate, and was then dried to give the title compound (9.2 mg, yield 11%).

Workup

concentrationThe reaction solution was concentrated
customwas subjected to separation and purification by column chromatography on silica gel
additionSubsequently, a hydrochloric acid-methanol mixed solution was added
customthe solvent was removed by distillation
customThe solid thus obtained
filtrationwas collected by filtration
washwas washed with ethyl acetate
customwas then dried

Sources & evidence

ORD record: ord-8484c208bb2f4d589fedafaea78de5b2
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560558B2

Reaction notes

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