反应详情

温度

60 °C

HCl.3H2O (45.05 g, 66.52 mmol) was charged into a reactor. Anhydrous N,N-dimethylformamide (DMF) (666 mL, 14.7 mL/g of IRT.HCl.3H2O, DMF water content NMT 300 ppm) was charged to the reactor. With slow agitation, the reactor was heated to 60° C. (jacket temperature). After the irinotecan (IRT) was fully dissolved (5-10 minutes), vacuum was slowly applied to reach 5-10 mbar and DMF was distilled off. When the volume of condensed distillate (DMF) reached 85-90% of the initial DMF charge, the vacuum was released. Heptane (1330 mL, 30.0 mL/g of IRT.HCl.3H2O, water content NMT 50 ppm) was introduced into the reactor and the jacket temperature was lowered to 50° C. Heptane was vacuum distilled (100-150 mbar) until the volume of the distillate was about 90% of the initial charge of heptane. Two more cycles of heptane distillation were carried out (2×1330 mL heptane charge and distillation). A solvent phase sample was taken from the reactor and was analyzed for DMF content using GC to ensure a DMF content of less than 3% w/w. (In the event the residual DMF was >3.0% w/w, a fourth azeotropic distillation cycle would be performed). The resultant slurry was used for the coupling reaction (Part 2).

1. distillationwas distilled off
2. customWhen the volume of condensed distillate (DMF)
3. additioncharge
4. customwas lowered to 50° C
5. distillationdistilled (100-150 mbar) until the volume of the distillate
6. additioninitial charge of heptane
7. distillationTwo more cycles of heptane distillation
8. addition(2×1330 mL heptane charge and distillation)
9. distillationa fourth azeotropic distillation cycle
10. customThe resultant slurry was used for the coupling reaction (Part 2)