反应详情

温度

52.5 °C

Triethylamine (140.8 g, 2.29 mol) was added at 25-30° C. to a solution of 3-amino-piperidine-2,6-dione hydrochloride (100 g, 0.61 mol) in N,N-dimethylformamide (800 ml). A solution of methyl 2-bromomethyl-3-nitro-benzoate (186.0 g, 1.13 mol) in acetonitrile (200 ml) was then added under stirring and a nitrogen atmosphere and the reaction mixture was heated to 50-55° C. for 8-10 hours. After completion of the reaction approximately 60% solvent was removed by distillation at 50-60° C. under reduced pressure (100 mbar). Water (1000 ml) was added to the residual mixture at 50-55° C. and stirred for 1 hour at this temperature. The resultant solid product was cooled to 25-30° C. and filtered. The solid was washed with water (500 ml) at 50-55° C., cooled at ambient temperature and filtered again. Finally the solid was washed with methanol (500 ml) at 50-55° C., cooled at 25-30° C. and filtered. The filtered solid product was dried at 50-55° C. under low pressure (200 mmHg) for 4 hours to give 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione as a purple to ash coloured solid.

1. customwas removed by distillation at 50-60° C. under reduced pressure (100 mbar)
2. additionWater (1000 ml) was added to the residual mixture at 50-55° C.
3. stirringstirred for 1 hour at this temperature
4. temperatureThe resultant solid product was cooled to 25-30° C.
5. filtrationfiltered
6. washThe solid was washed with water (500 ml) at 50-55° C.
7. temperaturecooled at ambient temperature
8. filtrationfiltered again
9. washFinally the solid was washed with methanol (500 ml) at 50-55° C.
10. temperaturecooled at 25-30° C.
11. filtrationfiltered
12. customThe filtered solid product was dried at 50-55° C. under low pressure (200 mmHg) for 4 hours