Continuous Synthesis of an Intermediate of Quinolone Antibiotic Drug Using Static Mixers

Abstract

In-line static mixer technology was employed in a continuous synthesis of a pharmaceutical intermediate of new quinolone antibiotics. The reaction of interest is the protection of amine with t-Boc, and it is characterized by a fast rate and relatively high exothermicity. The heat generated from the reaction can alter the reaction pathway or destroy the structure of the products. Reaction kinetics were derived from a series of batch measurements of heat flows using an RC1 reaction calorimeter. Results showed that the heat generated from the reaction initiated a mechanism for byproduct formation, and efficient mixing and heat removal with the static mixer led to reduced byproduct formation and promoted a high yield. On the basis of the reaction kinetics, a simple plug-flow reactor model was developed for this system.