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

HRID 2088941Notes

Reaction equation

Cl[C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C([O:15][CH:16]=[C:17]([C:23](OCC)=O)[C:18]([O:20]CC)=[O:19])C.C1(C)C=CC=CC=1>CCCCCC>[O:15]=[C:16]1[C:5]2[C:3](=[CH:2][CH:8]=[CH:7][C:6]=2[C:9]([F:12])([F:11])[F:10])[NH:4][CH:23]=[C:17]1[C:18]([OH:20])=[O:19]

Participants

Conditions

Temperature: 140 °C

Procedure

2-Chloro-5-(trifluoromethyl)aniline 2 (200 g, 1.023 mol), diethyl 2-(ethoxymethylene)malonate 3 (276 g, 1.3 mol) and toluene (100 mL) were combined under a nitrogen atmosphere in a three-neck, 1-L round bottom flask equipped with Dean-Stark condenser. The solution was heated with stirring to 140° C. and the temperature was maintained for 4 h. The reaction mixture was cooled to 70° C. and hexane (600 mL) was slowly added. The resulting slurry was stirred and allowed to warm to room temperature. The solid was collected by filtration, washed with 10% ethyl acetate in hexane (2×400 mL) and then dried under vacuum to provide a white solid (350 g, 94% yield) as the desired condensation product diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino) methylene) malonate 4. 1H NMR (400 MHz, DMSO-d6) δ 11.28 (d, J=13.0 Hz, 1H), 8.63 (d, J=13.0 Hz, 1H), 8.10 (s, 1H), 7.80 (d, J=8.3 Hz, 1H), 7.50 (dd, J=1.5, 8.4 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 4.17 (q, J=7.1 Hz,2H),1.27 (m, 6H).

Workup

temperatureThe solution was heated
temperaturethe temperature was maintained for 4 h
temperatureThe reaction mixture was cooled to 70° C.
stirringThe resulting slurry was stirred
temperatureto warm to room temperature
filtrationThe solid was collected by filtration
washwashed with 10% ethyl acetate in hexane (2×400 mL)
customdried under vacuum

Sources & evidence

ORD record: ord-7e8688059ecf4c969b761d6bd5c442d0
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436014B2

Reaction notes

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