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BATCH AND FLOW SYNTHESIS OF ATENOLOL® IN CAPILLARY MICROREACTORS

Grant number: 23/11154-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2023
Effective date (End): September 30, 2024
Field of knowledge:Engineering - Chemical Engineering - Chemical Technology
Principal Investigator:Mauri Sergio Alves Palma
Grantee:Fernanda Andrade Nocera
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The flow syntheses of Active Pharmaceutical Ingredients (APIs) have significant advantages over the usual batch process and, due to the high added value and low demand of drugs, there is a great potential for the flow syntheses in micro reactors. The main characteristics of micro reactors are excellent heat and mass transfer, high surface/volume ratio with laminar and plug flow. The micro reactors have been extensively used in the creation of chemical libraries of compounds with pharmacological potential, multiphase continuous syntheses, fast and exothermic reactions, in the intensification of chemical processes and chemical reactions involving dangerous, toxic or explosive compounds for them to be synthesized in smaller, more controlled and safe operation conditions. Some advantages of the APIs syntheses in flow micro reactor are the drastic reduction of reaction time due to the elimination of inefficient mixture, increase in the reaction yield and selectivity, and reduction of waste generation. The Chemical-Pharmaceutical industry is the major beneficiary of this new technology because the micro reactor can generate a higher variety of compounds with pharmacological potential in comparison to the regular batch process in less time, can reduce the time for the commercial production of a new API and can be produced in extremely small and compact industrial units. The objective of this project is to use capillary micro reactors for the flow synthesis of Atenolol®. One of the reactants that will be used is Epichlorohydrin which can be synthesized sustainably from glycerol, a by-product of the biodiesel synthesis, and is widely available in the Brazilian and world market besides being nontoxic and already largely used in pharmaceutical and food industry. This project is related to an ongoing PhD thesis on flow synthesis of biodiesel, under the supervision of Prof. Mauri Palma, initiated in 2021 in the Micro reactor Technology Laboratory-MRT-Lab (FBT/FCF/USP). In this project, we plan to synthesize Atenolol® in flow for the first time and determine the kinetics of the intermediate reactions and the best operation conditions for this synthesis, in batch and flow process. This research project will be developed within the scope of an ongoing research financed by FAPESP, grant number 2022/16165-8, entitled "Flow synthesis of Atenolol®, Metoprolol®, and Ranolazine® using derivatives of glycerol as reagents", running from April/2023 to March/2025.

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