Dimethylformamide → [3-(4-chloro-2-fluorobenzyl)-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy]acetic Acid Methyl Ester

HRID 2266595Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8](=[O:28])[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[F:27])=[C:10]([CH2:17][CH3:18])[NH:11]2.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Cl[C:42](OC(=O)C)([F:44])[F:43]>O>[CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:28][CH:42]([F:44])[F:43])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[F:27])[C:10]([CH2:17][CH3:18])=[N:11]2

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of [3-(4-chloro-2-fluorobenzyl)-2-ethyl-8-fluoro-4-oxo-1,4-dihydroquinolin-5-yloxy]acetic acid methyl ester (0.20 g), N,N-dimethylformamide (3.0 mL), potassium carbonate (0.20 g) and acetic acid chlorodifluoromethyl ester (0.15 mL) was stirred at 80° C. for 4 days. The mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and the solvent removed under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and dichloromethane (1:4 by volume) gave title compound, 0.071 g.

Workup

extractionextracted with ethyl acetate
washThe combined extracts were washed with saturated aqueous sodium chloride solution
dry with materialdried over magnesium sulfate
customthe solvent removed under reduced pressure
customPurification of the residue by column chromatography on silica gel
washeluting with a mixture of cyclohexane and dichloromethane (1:4 by volume)

Sources & evidence

ORD record: ord-fb276da6c8f64cc58c987b2c020ae996
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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