3-(3-Chloro-2-fluoro-phenylamino)-3-phenyl-acrylic acid ethyl ester → 7-Chloro-8-fluoro-2-phenylquinolin-4(1H)-one

HRID 1028830Notes

Reaction equation

C(O[C:4](=[O:22])[CH:5]=[C:6]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[F:21])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C>O>[Cl:20][C:16]1[C:15]([F:21])=[C:14]2[C:19]([C:4](=[O:22])[CH:5]=[C:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:13]2)=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 175 °C

Procedure

3-(3-Chloro-2-fluoro-phenylamino)-3-phenyl-acrylic acid ethyl ester (9.2 g, 0.029 mole) and polyphosphoric acid (160 mL, 3.0 mole) were combined and mechanically stirred under nitrogen at 175° C. external temperature for 40 minutes. While still hot, the reaction was poured over 800 mL of stirring ice-water rinsing with water. The mixture was a fine suspension, and was allowed to stir overnight. After stirring overnight, the mixture was filtered to collect the solid. The solid was washed with 4×150 mL water, and then with 4×150 mL of 4:1 ether/methanol. The solid was placed in the vacuum oven at 45° C. for 4 h and afforded the title compound as an off white product; 1H NMR (DMSO-d6, 400 MHz) δ 6.58 (bs, 1H), 7.50-7.54 (d of d, 1H, J=6.6 Hz & J=8.9 Hz), 7.60-7.64 (m, 3H), 7.82-7.84 (m, 2H), 8.07-8.09 (d of d, 1H, J=1.5 Hz & J=8.7 Hz); MS (ES+): 274.03 (100) [MH+], 275.99 (30) [(M+2)H+]. LCMS tR=2.97 min (OpenLynx, polar—5 min).

Workup

stirringto stir overnight
stirringAfter stirring overnight
filtrationthe mixture was filtered
customto collect the solid
washThe solid was washed with 4×150 mL water
waitThe solid was placed in the vacuum oven at 45° C. for 4 h

Sources & evidence

ORD record: ord-15b75057a9af4e14b43f5109789eaa70
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735405B2

Reaction notes

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