Sodium Hydroxide → 4-Oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid

HRID 1908218Notes

Reaction equation

[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[C:12]([F:15])([F:14])[F:13])[NH:5][CH:4]=[C:3]1[C:16]([O:18]CC)=[O:17].[OH-].[Na+]>[Pd]>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[C:12]([F:15])([F:13])[F:14])[NH:5][CH:4]=[C:3]1[C:16]([OH:18])=[O:17]

Participants

Conditions

Temperature: 80 °C

Procedure

Ethyl 4-oxo-5-(trifluoromethyl)-1H-quinoline-3-carboxylate 16 (58 g, 0.2 mol, crude reaction slurry containing Pd/C) was suspended in NaOH (814 mL of 5 M, 4.1 mol) in a 1-L flask with a reflux condenser and heated at 80° C. for 18 h, followed by further heating at 100° C. for 5 h. The reaction was filtered warm through packed Celite to remove Pd/C and the Celite was rinsed with 1 N NaOH. The filtrate was acidified to about pH 1 to obtain a thick, white precipitate. The precipitate was filtered then rinsed with water and cold acetonitrile. The solid was then dried under vacuum to provide 4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid 17 as a white solid (48 g, 92% yield). 1H NMR (400.0 MHz, DMSO-d6) δ 15.26 (s, 1H), 13.66 (s, 1H), 8.98 (s, 1H), 8.13 (dd, J=1.6, 7.8 Hz, 1H), 8.06-7.99 (m, 2H).

Workup

temperatureby further heating at 100° C. for 5 h
filtrationThe reaction was filtered
temperaturewarm
customto remove Pd/C
washthe Celite was rinsed with 1 N NaOH
customto obtain a thick, white precipitate
filtrationThe precipitate was filtered
washthen rinsed with water and cold acetonitrile
customThe solid was then dried under vacuum

Sources & evidence

ORD record: ord-c8047a497c014619b8916691d3bc9f48
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598205B2

Reaction notes

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