1,4-Dioxane → [3-(4-chloro-2-fluorobenzyl)-2-ethyl-8-fluoro-4-oxo-1,4-dihydroquinolin-5-yloxy]acetic Acid Methyl Ester

HRID 2266594Notes

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:16][C:17](=O)[CH:18]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[F:31])[C:19](=O)[CH2:20][CH3:21].O1CCOCC1>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:17](=[O:16])[C:18]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[F:31])=[C:19]([CH2:20][CH3:21])[NH:13]2

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of (3-amino-4-fluorophenoxy)acetic acid methyl ester (0.80 g), 2-(4-chloro-2-fluorobenzyl)-3-oxopentanoic acid methyl ester (1.4 g), polyphosphoric acid (5 g) and dioxane (10 mL) was heated at 120° C. for 23 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined extracts were washed with water, dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (3:7 to 7:10 by volume) to afford title compound, 0.20 g.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with ethyl acetate
washThe combined extracts were washed with water
dry with materialdried over magnesium sulfate
customthe solvent removed under reduced pressure
customThe residue was purified by column chromatography on silica gel
washeluting with a mixture of ethyl acetate and cyclohexane (3:7 to 7:10 by volume)

Sources & evidence

ORD record: ord-c8b5a7e1e59e4edeb5b68fa81085133f
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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