SYNTHESIS OF N-(2,6-DIMETHYLPHENYL)-CHLOROACETAMIDE IN BATCH AND FLOW IN MICROREACTORS

• Grant number: 24/20177-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Samuel Gustavo Alves de Almeida Vieira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This project aims to synthesize N-(2,6-dimethylphenyl)chloroacetamide, a key intermediate in the synthesis route of Ranolazine, a medication used in the treatment of angina, characterized by temporary chest pain due to a lack of oxygen in the cardiac muscle. Ranolazine is approved as an antianginal for patients with stable coronary artery disease and is often administered in combination with other medications such as Atenolol, Amlodipine, or Diltiazem. The work aims to transition one of the four reactions necessary for the synthesis of Ranolazine from the conventional batch process to a flow process using a capillary microreactor. The optimal operational conditions for the batch process will be determined, examining the influence of temperature, solvent, concentration of the reaction medium, and concentration of the base on the conversion of the limiting reagent into the target product, aiming to maximize conversion, yield, and selectivity with the shortest reaction time. After determining the best operational conditions in the batch process, this reaction will be transferred to the flow process, which offers significant advantages over batch processing, such as higher reaction speed, conversion, yield, selectivity, and enhanced safety when handling toxic reagents and products. Once these conditions are established in the microreactor, the reaction kinetics will also be determined, including thermodynamic parameters such as Ea, ¿H*, ¿S*, and ¿G*; additionally, a comparative study of production and productivity between batch and flow processes will be conducted, aiming to estimate the equivalent number of parallel microreactors needed to achieve the same production as in batch.