SYNTHESIS OF RANOLAZINE INTERMEDIATE IN BATCH PROCESS AND FLOW IN MICROREACTORS AND MATHEMATICAL SIMULATION OF THE PROCESSES

• Grant number: 23/16195-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2024
• End date: April 30, 2025
• Field of knowledge: Engineering - Chemical Engineering - Chemical Process Industries
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Jimmy dos Santos Barros Araujo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The chemical-pharmaceutical industries in Brazil use batch reactors for synthesis processes, however, this process has limitations regarding temperature, pressure and mixing efficiency. The use of microreactors in the chemical-pharmaceutical industries reduces the impact generated by processes with a substantial reduction in waste. Furthermore, they provide a significant increase in mass and heat transfer rates, which results in an easily controllable process allowing greater safety, when working with toxic reagents and products, yield and selectivity compared to batch reactors. Considering these characteristics, it is essential that Microreactor Technology (TMR) is more widespread in the chemical-pharmaceutical industry, as it is necessary to increase the production scale to meet market demand in a faster and more effective way and, thus, recover the investment applied during research. The drug Ranolazine is used to treat Angina, which is temporary chest pain or a feeling of pressure that occurs when the heart muscle is not receiving enough oxygen. Ranolazine has been approved as an antianginal medication for the treatment of patients with stable coronary artery disease, usually administered along with other antianginal medications such as Atenolol, Amlodipine, or Diltiazem. The present work aims to transpose an intermediate reaction of the four necessary for the synthesis of Ranolazine from the usual process in the chemical-pharmaceutical industry (batch) to the flow process in a microreactor. The best operational conditions in the batch process will be determined in terms of temperature, solvent, catalyst, catalyst concentration, total concentration of the reaction medium in the conversion of the limiting reagent, yield and product selectivity. In the flow process, the influence of the flow's average residence time will also be determined. In this project, mathematical simulation of the batch process and the flow process in a capillary microreactor will also be carried out. This scientific initiation project will be developed within the scope of individual research assistance "Synthesis of Atenolol®, Metoprolol® and Ranolazine® in flow using glycerol derivatives as reagents", FAPESP process n. 2022/16165-8, effective from 04/01/2023 to 03/31/2025.