反应详情

Ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate (5A) (1200 g, 3.754 mol) was charged into a reaction vessel followed by the addition of 2-popanol (1.200 L) and water (7.200 L) and stirred. Sodium hydroxide (600.6 g, 7.508 mol) and water (1.200 L) were mixed and allowed to cool to room temperature. The resulting mixture was charged into the reaction vessel and then was heated to 80° C. with stirring for 3.5 h to generate a dark, homogenous mixture. After an additional hour, acetic acid (9.599 L of 20% w/v, 31.97 mol) was added via dropping funnel over 45 min. The reaction mixture was cooled with stirring to 22° C. at a rate of 6° C./h. The resulting solid was filtered and washed with water (3 L) to generate a wet cake (1436 g). The filtrate was dried in a vacuum oven with a nitrogen bleed over Drierite® to generate 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid (5B) as a brown solid (1069 g). The 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid (5B) was purified by slurrying in 1.5 L methanol and stirring for 6 h. It was then filtered and dried to furnish 968.8 g of purified 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid (5B).

1. additionThe resulting mixture was charged into the reaction vessel
2. temperaturewas heated to 80° C.
3. stirringwith stirring for 3.5 h
4. waitAfter an additional hour
5. customover 45 min
6. temperatureThe reaction mixture was cooled
7. stirringwith stirring to 22° C. at a rate of 6° C./h
8. filtrationThe resulting solid was filtered
9. washwashed with water (3 L)
10. customThe filtrate was dried in a vacuum oven with a nitrogen
11. customThe 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid (5B) was purified
12. stirringstirring for 6 h
13. filtrationIt was then filtered
14. customdried