Ethyl 2-(4-chlorobenzyl)acetoacetate → [3-(4-Chlorobenzyl)-8-fluoro-2-methyl-4-oxo-1,4-dihydroquinolin-5-yloxy]acetic acid methyl ester

HRID 2266479Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([NH2:13])[CH:7]=1.C([O:17][C:18](=O)[CH:19]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:20](=O)[CH3:21])C>O>[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:7]=1[C:18](=[O:17])[C:19]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=1)=[C:20]([CH3:21])[NH:13]2

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of (3-amino-4-fluorophenoxy)acetic acid methyl ester (0.50 g), 2-(4-chlorobenzyl)-3-oxobutyric acid ethyl ester (7.4 g) and polyphosphoric acid (1.1 g) was heated at 130° C. for 2 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined extracts were washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (19:1 by volume) to afford title compound, 0.29 g.

Workup

temperatureThe mixture was cooled to room temperature
extractionextracted with ethyl acetate
washThe combined extracts were washed with water
dry with materialdried over sodium sulfate
customThe solvent was removed under reduced pressure
customthe residue purified by column chromatography on silica gel
washeluting with a mixture of dichloromethane and methanol (19:1 by volume)

Sources & evidence

ORD record: ord-7d2777005a4e4652a22216ab28b7c645
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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