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Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene
We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491450/ https://www.ncbi.nlm.nih.gov/pubmed/34631154 http://dx.doi.org/10.1007/s41981-021-00205-x |
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author | Ivanova, Maria Legros, Julien Poisson, Thomas Jubault, Philippe |
author_facet | Ivanova, Maria Legros, Julien Poisson, Thomas Jubault, Philippe |
author_sort | Ivanova, Maria |
collection | PubMed |
description | We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of the obtained alcohol into ketone followed by condensation with 4-sulfamidophenylhydrazine afforded the targeted drug with full regioselectivity. It is noteworthy that the quality of these flow reactions (50% overall yield within 1 h cumulated residence time over 3 steps) directly furnished the target API and intermediates with excellent purity. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41981-021-00205-x. |
format | Online Article Text |
id | pubmed-8491450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-84914502021-10-05 Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene Ivanova, Maria Legros, Julien Poisson, Thomas Jubault, Philippe J Flow Chem Communications We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of the obtained alcohol into ketone followed by condensation with 4-sulfamidophenylhydrazine afforded the targeted drug with full regioselectivity. It is noteworthy that the quality of these flow reactions (50% overall yield within 1 h cumulated residence time over 3 steps) directly furnished the target API and intermediates with excellent purity. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41981-021-00205-x. Springer International Publishing 2021-10-05 2022 /pmc/articles/PMC8491450/ /pubmed/34631154 http://dx.doi.org/10.1007/s41981-021-00205-x Text en © Akadémiai Kiadó 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Communications Ivanova, Maria Legros, Julien Poisson, Thomas Jubault, Philippe Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title | Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title_full | Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title_fullStr | Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title_full_unstemmed | Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title_short | Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene |
title_sort | continuous flow synthesis of celecoxib from 2-bromo-3,3,3-trifluoropropene |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491450/ https://www.ncbi.nlm.nih.gov/pubmed/34631154 http://dx.doi.org/10.1007/s41981-021-00205-x |
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