Flow Synthesis of a Thiazolidine Drug Intermediate in Capillary Microreactors

被引：8

作者：

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
]}

机构：

[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

来源：

CHEMICAL ENGINEERING & TECHNOLOGY | 2019年 / 42卷 / 02期

基金：

巴西圣保罗研究基金会;

关键词：

Batch-to-continuous transfer; Glitazones; Kinetics; Microreactor technology; Thermodynamics; CONDENSATION REACTION; TECHNOLOGY; 2,4-THIAZOLIDINEDIONE; ADDUCTS; MOIETY;

D O I：

10.1002/ceat.201800473

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

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.

引用

页码：465 / 473

页数：9

共 40 条

[1] Synthesis of Celecoxib, Mavacoxib, SC-560, Fluxapyroxad, and Bixafen Enabled by Continuous Flow Reaction Modules [J].

Britton, Joshua ;

Jamison, Timothy F. .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2017, 2017 (44) :6566-6574

[2] Multi-step continuous-flow synthesis [J].

Britton, Joshua ;

Raston, Colin L. .

CHEMICAL SOCIETY REVIEWS, 2017, 46 (05) :1250-1271

[3] Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones [J].

Bruno, G ;

Costantino, L ;

Curinga, C ;

Maccari, R ;

Monforte, F ;

Nicolò, F ;

Ottanà, R ;

Vigorita, MG .

BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (04) :1077-1084

[4]

Byrne F.P., 2016, Sustainable Chemical Processes, V4, DOI [10.1186/s40508-016-0051-z, DOI 10.1186/S40508-016-0051-Z]

[5] Process Intensified Flow Synthesis of 1H-4-Substituted Imidazoles: Toward the Continuous Production of Daclatasvir [J].

Carneiro, Paula F. ;

Gutmann, Bernhard ;

de Souza, Rodrigo O. M. A. ;

Oliver Kappe, C. .

ACS SUSTAINABLE CHEMISTRY & ENGINEERING, 2015, 3 (12) :3445-3453

[6]

Clesceri L. S., 1999, STANDARD METHODS EXA, P1181

[7] Perspective on solvent use in the pharmaceutical industry [J].

Constable, David J. C. ;

Jimenez-Gonzalez, Conchita ;

Henderson, Richard K. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2007, 11 (01) :133-137

[8]

Da Silva Pinheiro D., 2017, MOJ Bioorganic Org. Chem, V1, P122, DOI [10.15406/mojboc.2017.01.00022, DOI 10.15406/MOJBOC.2017.01.00022]

[9] A three step continuous flow synthesis of the biaryl unit of the HIV protease inhibitor Atazanavir [J].

Dalla-Vechia, Luciana ;

Reichart, Benedikt ;

Glasnov, Toma ;

Miranda, Leandro S. M. ;

Kappe, C. Oliver ;

de Souza, Rodrigo O. M. A. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2013, 11 (39) :6806-6813

[10] Regiospecific reduction of 5-benzylidene-2,4-thiazolidinediones and 4-oxo-2-thiazolidinethiones using lithium borohydride in pyridine and tetrahydrofuran [J].

Giles, RG ;

Lewis, NJ ;

Quick, JK ;

Sasse, MJ ;

Urquhart, MWJ ;

Youssef, L .

TETRAHEDRON, 2000, 56 (26) :4531-4537

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