Direct amidation of acids in a screw reactor for the continuous flow synthesis of amides.

A simple and efficient solvent-free protocol for continuous flow synthesis of amides at room temperature is developed using easily available starting materials. -(3-Dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC.HCl) was used as the reagent for the formation of an amide bond without using any metal catalyst or additives.

Multi-Step Synthesis of Miltefosine: Integration of Flow Chemistry with Continuous Mechanochemistry.

Herein we report for the first time, an advanced continuous flow synthesis of the blockbuster Leishmaniasis drug miltefosine from simple starting materials by a sequence involving four steps of chemical transformation including a continuous mechanochemical step. First three reaction steps were performed in simple tubular reactors in a telescopic mode, while in the last step the product precipitated from the 3 step was used for a continuous mechanochemical synthesis of miltefosine. When compared to a typical batch protocol that takes 15 h, miltefosine was obtained in 58 % overall yield in flow synthesis mode at the laboratory scale in a total residence time 34 min at synthesis rate of 10 g/hr, which is sufficient to treat 4800 patients per day.