Dimethylformamide → Camptosar

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).