Diethyl (ethoxymethylene)malonate → HCID 178418765, compound

Temperature

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)

ORD record

ord-ff960a95ab924ac1906d44af0404b308

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378102B2