Dimethylformamide → [2-difluoromethoxy-8-fluoro-3-(4-fluorobenzyl)-4-methylquinolin-5-yloxy]acetic Acid Methyl Ester

HRID 2266556Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:27])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:26])=[C:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[C:10](=[O:17])[NH:11]2.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Cl[C:40](OC(=O)C)([F:42])[F:41]>O>[CH3:1][O:2][C:3](=[O:27])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:26])=[C:9]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)[C:10]([O:17][CH:40]([F:42])[F:41])=[N:11]2

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of [8-fluoro-3-(4-fluorobenzyl)-4-methyl-2-oxo-1,2-dihydroquinolin-5-yloxy]acetic acid methyl ester (0.48 g), N,N-dimethylformamide (6.0 mL), potassium carbonate (0.72 g) and acetic acid chlorodifluoromethyl ester (1.7 mL) was stirred at 70° C. for 5 days. The mixture was diluted with Water, extracted with ethyl acetate and the combined extracts washed with water and then dried over magnesium sulfate. The solvent was removed under reduced pressure and purification of the residue by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (1:6 by volume), followed by washing with diethyl ether gave title compound as a white solid, 0.29 g.

Workup

extractionextracted with ethyl acetate
washthe combined extracts washed with water
dry with materialdried over magnesium sulfate
customThe solvent was removed under reduced pressure and purification of the residue by column chromatography on silica gel
washeluting with a mixture of ethyl acetate and cyclohexane (1:6 by volume)
washby washing with diethyl ether

Sources & evidence

ORD record: ord-8bdeba77f22a4907abebe6764d1675f8
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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