Continuous flow upgrading of glycerol toward oxiranes and active pharmaceutical ingredients thereof

The progressive depletion of fossil resources and a global environmental awareness stimulates research toward a transition for more sustainable supplies. Glycerol, which is nowadays obtained as a by-product of the biodiesel production, presents a significant industrial potential and can be upgraded in a large variety of value-added building blocks. We present herein a robust multi-module continuous flow procedure for the valorization of glycerol towards active pharmaceutical ingredients (APIs) through the intermediate formation of epichlorohydrin. The first module is dedicated to the valorization of glycerol into oxiranes by a hydrochlorination/dechlorination concatenated sequence involving economically and environmentally favorable conditions, an organocatalyst and an in-line separation of the two products. Finally, biobased epichlorohydrin is further utilized for the preparation of β-amino alcohol APIs including propranolol (hypertension, WHO essential), naftopidil (prostatic hyperplasia) and alprenolol (angina pectoris) within a concatenable Williamson/aminolysis sequence using a FDA class 3 solvent (DMSO).