反应详情

温度

27.5 °C

4-methyl-3-nitroaniline (30.0 g, 0.197 mol) is added to a mixture of tetrahydrofuran (120 ml) and N-ethyl-N,N-diisopropyl-amine at 23-25° C. over a period of 5 to 10 min. To this solution chloromethyl-benzoylchloride (38.4 g, 0.20 mol) dissolved in tetrahydrofuran (35 ml) is added over a period of 60-65 min maintaining a temperature of 25-30° C. The reaction mixture is stirred at this temperature for 30 min and then added to N-methylpiperazine (138.2 g, 1.38 mol) over a period of 60 to 90° C. maintaining a temperature of 25-30° C. The resulting suspension is stirred at this temperature for 60 min. Tetrahydrofurane is distilled of at 50° C. under reduced pressure. At the end of the distillation the temperature is adjusted to 45-48° C. and water (300 ml) Is added over a period of 45-60 min at this temperature. The resulting suspension is cooled to 23° C. and stirred for 60 min. The suspension is filtered, the filtercake washed with water (225 ml) and dried in vacuo to give 69.2 g of the title compound (95% of theory) as an of-white powder (99.5% area by HPLC).

1. additionis added over a period of 60-65 min
2. temperaturemaintaining a temperature of 25-30° C
3. stirringThe resulting suspension is stirred at this temperature for 60 min
4. distillationTetrahydrofurane is distilled of at 50° C. under reduced pressure
5. distillationAt the end of the distillation the temperature
6. customis adjusted to 45-48° C.
7. additionwater (300 ml) Is added over a period of 45-60 min at this temperature
8. temperatureThe resulting suspension is cooled to 23° C.
9. stirringstirred for 60 min
10. filtrationThe suspension is filtered
11. washthe filtercake washed with water (225 ml)
12. customdried in vacuo