Flow Synthesis of a Thiazolidine Drug Intermediate in Capillary Microreactors

Author(s)

de Oliveira Silva, Renan Rodrigues ^[1] ; Cuesta Calvo, Paulo Victor ^[1] ; da Silva, Milena Fernandes ^[2] ; Solisio, Carlo ^[3] ; Converti, Attilio ^[3] ; Alves Palma, Mauri Sergio ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Biochem & Pharmaceut Technol, Ave Prof Lineu Prestes 580, Bloco 16, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Pernambuco, Biosci Ctr, Ave Prof Moraes Rego 1235, Cidade Univ, BR-50670901 Recife, PE - Brazil

^[3] Genoa Univ, Dept Civil Chem & Environm Engn, Pole Chem Engn, Via Opera Pia 15, I-16145 Genoa - Italy

• Document type: Journal article
• Source: CHEMICAL ENGINEERING & TECHNOLOGY; v. 42, n. 2, p. 465-473, FEB 2019.
• Web of Science Citations: 1

Abstract

Microreactor technology can help to reduce the time to market new drugs. It was applied to produce (Z)-5-benzylidenethiazolidine-2,4-dione, a heterocyclic intermediate in the synthesis of various drugs. Ethanol was the optimum solvent and piperidine the best catalyst in the batch process. The continuous/microreactor process exhibited a much better performance than the batch process. The productivity, which was strongly influenced by solvent and temperature, reached a maximum at 160 degrees C using methanol as solvent. A kinetic/thermodynamic study indicated that the reaction followed the second-order model and allowed estimating its main thermodynamic parameters. A product recovery protocol was finally proposed. The microreactor proved an efficient alternative to the batch reactor in scaling up the production of active pharmaceutical ingredients. (AU)

• FAPESP's process: 14/07757-2 - Micro-reactors in the synthesis of pharmaceuticals
• Grantee: Mauri Sergio Alves Palma
• Support Opportunities: Regular Research Grants