反应详情

温度

105 °C

A mixture of 2-[(3,4-dichlorobenzyl)amino]ethanol (400 g) and (S)-2-(oxiran-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (399.6 g) in toluene (1150 ml) was stirred and heated at 103-107° C. under nitrogen. After 22.5 h the mixture was cooled to <60° C. and charged with tetrahydrofuran (2800 ml). Triphenyl phosphine (548 g) was added and the mixture was stirred until all the solid had dissolved, then cooled to 5-9° C. Diisopropylazodicarboxylate (412 ml) was then added over 70 min maintaining the temperature at <12°. The mixture was warmed to 21-25° and stirred for 1.5 h. The reaction mixture was concentrated by distillation to a final volume of 2800 ml. Methanol (2800 ml) was added and the concentration repeated to a volume of 2800 ml. More methanol (2000 ml) was added and the mixture was heated to 55°. After 0.75 h the slurry was cooled to 18° and then after a further 1 h the product was collected. The bed was washed with methanol (2×1200 ml) and then dried in vacuo at 40° to give the title compound (526.9 g).

1. temperatureAfter 22.5 h the mixture was cooled to <60° C.
2. stirringthe mixture was stirred until all the solid
3. dissolutionhad dissolved
4. temperaturecooled to 5-9° C
5. temperaturemaintaining the temperature at <12°
6. temperatureThe mixture was warmed to 21-25°
7. stirringstirred for 1.5 h
8. concentrationThe reaction mixture was concentrated by distillation to a final volume of 2800 ml
9. additionMethanol (2800 ml) was added
10. concentrationthe concentration
11. additionMore methanol (2000 ml) was added
12. temperaturethe mixture was heated to 55°
13. temperatureAfter 0.75 h the slurry was cooled to 18°
14. customafter a further 1 h the product was collected
15. washThe bed was washed with methanol (2×1200 ml)
16. customdried in vacuo at 40°