Potassium Carbonate → [4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-fluorobenzyl)quinolin-5-yloxy]acetic Acid Methyl Ester

HRID 2266550Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8](=[O:27])[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=[C:10]([CH2:17][CH3:18])[NH:11]2.C(=O)([O-])[O-].[K+].[K+].Cl[C:36](OC(=O)C)([F:38])[F:37]>O>[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:27][CH:36]([F:38])[F:37])=[C:9]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1)[C:10]([CH2:17][CH3:18])=[N:11]2

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of [2-ethyl-8-fluoro-3-(4-fluorobenzyl)-4-oxo-1,4-dihydroquinolin-5-yloxy]acetic acid methyl ester (1.5 g), N/N-dimethylformamide (30 mL), potassium carbonate (5.2 g) and acetic acid chlorodifluoromethyl ester (5.5 mL) was stirred at 70° C. for 4 days. The mixture was diluted with water and extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (3:1 by volume) to afford title compounds, 0.50 g.

Workup

extractionextracted with ethyl acetate
dry with materialThe combined extracts were dried over sodium sulfate
customthe solvent removed under reduced pressure
customThe residue was purified by column chromatography on silica gel
washeluting with a mixture of cyclohexane and ethyl acetate (3:1 by volume)
customto afford title compounds, 0.50 g

Sources & evidence

ORD record: ord-6abe094a6f414a35971c3b9a2fb659ce
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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