反应详情

温度

125 °C

Diethyl ethoxymethylenemalonate (677 g, 3.13 moles (mol)) was added to 3-bromoaniline (491 g, 2.85 mol) over a period of one hour, the temperature rose to 60° C. during the addition. The reaction was then heated at 115° C. for 30 minutes, 125° C. for 30 minutes, and 140° C. for 15 minutes while ethanol was distilled from the reaction. The reaction temperature was adjusted to 130° C., and the reaction mixture was added over a period of 45 minutes to heated DOWTHERM A heat transfer fluid (5 liters (L), 250° C.) while maintaining the temperature of the heat transfer fluid between 242° C. and 250° C. A precipitate formed at the end of the addition. The reaction mixture was heated at about 250° C. for one hour and then cooled to 80° C. Concentrated hydrochloric acid (500 mL) was added, and the reaction mixture was heated at 110° C. for five hours, 125° C. for two hours, and 150° C. for an addition two hours, and then allowed to cool to room temperature overnight. The mixture was then heated to 200° C. over a period of two hours, further heated to 250° C., maintained at 250° C. for one hour, and allowed to cool to room temperature. A precipitate was present and was isolated by filtration, washed sequentially with heptane (2 L), ethanol (1 L), and diethyl ether (1 L) to provide 604 g of 7-bromo quinolin-4-ol as a dark red solid.

1. additionthe temperature rose to 60° C. during the addition
2. distillation140° C. for 15 minutes while ethanol was distilled from the reaction
3. customwas adjusted to 130° C.
4. additionthe reaction mixture was added over a period of 45 minutes
5. temperatureto heated DOWTHERM A
6. temperatureheat transfer fluid (5 liters (L), 250° C.)
7. temperaturewhile maintaining the temperature of the heat transfer fluid between 242° C. and 250° C
8. customA precipitate formed at the end of the addition
9. temperatureThe reaction mixture was heated at about 250° C. for one hour
10. temperaturecooled to 80° C
11. temperaturethe reaction mixture was heated at 110° C. for five hours, 125° C. for two hours
12. addition150° C. for an addition two hours
13. temperatureto cool to room temperature overnight
14. temperatureThe mixture was then heated to 200° C. over a period of two hours
15. temperaturefurther heated to 250° C.
16. temperaturemaintained at 250° C. for one hour
17. temperatureto cool to room temperature
18. customwas isolated by filtration
19. washwashed sequentially with heptane (2 L), ethanol (1 L), and diethyl ether (1 L)