Continuous-Flow Sequential Schotten-Baumann Carbamoylation and Acetate Hydrolysis in the Synthesis of Capecitabine

摘要

Capecitabine is an important anticancer drug whose synthesis comprises late-stage carbamoylation and ester hydrolysis. Herein we report the use of the Schotten-Baumann reaction in order to perform these transformation in one pot both in batch and under continuous flow. In batch, capecitabine was obtained in 82% yield in 5 h, while under continuous flow it was obtained in 81% yield in 30 min. This one-pot reaction reduces the chemical waste produced, labor, time, and cost and additionally comprises the use of environmentally friendly solvents and reagents as well as energy-efficient and safe methods, all of which fulfill the requirements of a green process.