反应详情

温度

82.5 °C

1800 kg (3 mol) of 1-[(4-methylquinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-phthalimidopiperidin-1-yl)-xanthine are heated to 80-85° C. in 18 litres of toluene. Subsequently, 1.815 litres (30 mol) of ethanolamine are added to the suspension at 75-80° C. To complete the reaction, the mixture is stirred at 80-85° C. for 2 hours, in the course of which the solids go into solution. Subsequently, the phases are separated. The ethanolamine phase is washed twice with warm toluene (4 litres each time). The combined toluene phases are washed twice with 8 litres each time of water at 75-80° C. From the toluene phase, 22 litres of toluene are distilled off under reduced pressure. 4 litres of tert.-butyl methyl ether are metered at 40-50° C. to the resulting suspension and subsequently cooled to 0-5° C. The product is isolated by filtration, washed with tert.-butyl methyl ether and suction-dried. The moist crude substance is subsequently heated to reflux with 5 times the amount of absolute ethanol and the hot solution is clarified by filtration through activated carbon. After the filtrate has been cooled to 20° C. and crystallization has set in, it is diluted to double the volume with tert.-butyl methyl ether. The suspension is cooled to 2° C., stirred for a further 2 hours, filtered with suction and dried at 45° C. in a vacuum drying cabinet.

1. customthe reaction
2. customSubsequently, the phases are separated
3. washThe ethanolamine phase is washed twice with warm toluene (4 litres each time)
4. washThe combined toluene phases are washed twice with 8 litres each time of water at 75-80° C
5. distillationFrom the toluene phase, 22 litres of toluene are distilled off under reduced pressure
6. customare metered at 40-50° C. to the resulting suspension
7. temperaturesubsequently cooled to 0-5° C
8. customThe product is isolated by filtration
9. washwashed with tert.-butyl methyl ether
10. customsuction-dried
11. temperatureThe moist crude substance is subsequently heated
12. temperatureto reflux with 5 times the amount of absolute ethanol
13. filtrationthe hot solution is clarified by filtration through activated carbon
14. temperatureAfter the filtrate has been cooled to 20° C.
15. customcrystallization
16. additionis diluted
17. temperatureThe suspension is cooled to 2° C.
18. stirringstirred for a further 2 hours
19. filtrationfiltered with suction
20. customdried at 45° C. in a vacuum
21. customdrying cabinet