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- 저자 : Mikael Vitor Rodrigues Lima (검색결과 1 건)
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Renan Rodrigues de Oliveira Silva,Paulo Victor Cuesta Calvo,Christian Adrian Merfels,Mikael Vitor Rodrigues Lima,Harrson S. Santana,Attilio Converti,Mauri Sergio Alves Palma 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.116 No.-
Continuous flow synthesis in microreactors has been integrated into chemical-pharmaceutical industryin recent years as an alternative to the batch process due to its advantages, especially process intensification,which can reduce the time for a new drug to be placed on the market on a large scale. This workaimed to transpose the synthesis of Lobeglitazone, a drug employed in the treatment of diabetes mellitustype 2, from batch to flow process in a microreactor as well as to determine the reaction kinetics of eachstep. The synthesis was carried out in five-steps, being synthesized intermediates 4-chloro-6-(4-methoxyphenoxy)pyrimidine (I1), 2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethanol (I2), 4-(2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzaldehyde (I3), 5-[4-(2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzylidene]thiazolidine-2,4-dione (I4) andLobeglitazone. Intermediates I1 and I4 were synthesized in flow, while I4 was synthesized either in a continuousflow multistep synthesis or in a one-pot batch process. The flow syntheses of I1, I2 and I4 showed28.0 %, 61.8 % and 32.0 % yields at 25, 160 and 120 C, respectively, while the yield of I3 in batch processwas 73.3 % at 60 C. In one-pot batch process and continuous flow multistep synthesis, I2 was obtainedwith 13 and 16 % yields, respectively. These preliminary results constitute a starting point for the synthesisof this drug in flow on an industrial scale, with the aim of improving reaction performance using thisnew technology.
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