Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil

Detalhes bibliográficos
Autor(a) principal: Vaz, Artur
Data de Publicação: 2023
Outros Autores: Lopes, João Luis Callegari, Clososki, Giuliano Cesar
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/213470
Resumo: Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, “slug-flow” regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.
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spelling Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug RemifentanilRemifentanilOpioidsOrganic synthesisContinuous flow synthesisRemifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, “slug-flow” regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2023-06-22info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/21347010.1590/s2175-97902023e22764 Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023)Brazilian Journal of Pharmaceutical Sciences; v. 59 (2023)Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/213470/195518Copyright (c) 2023 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessVaz, ArturLopes, João Luis CallegariClososki, Giuliano Cesar2023-06-22T13:57:34Zoai:revistas.usp.br:article/213470Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-06-22T13:57:34Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
title Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
spellingShingle Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
Vaz, Artur
Remifentanil
Opioids
Organic synthesis
Continuous flow synthesis
title_short Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
title_full Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
title_fullStr Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
title_full_unstemmed Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
title_sort Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil
author Vaz, Artur
author_facet Vaz, Artur
Lopes, João Luis Callegari
Clososki, Giuliano Cesar
author_role author
author2 Lopes, João Luis Callegari
Clososki, Giuliano Cesar
author2_role author
author
dc.contributor.author.fl_str_mv Vaz, Artur
Lopes, João Luis Callegari
Clososki, Giuliano Cesar
dc.subject.por.fl_str_mv Remifentanil
Opioids
Organic synthesis
Continuous flow synthesis
topic Remifentanil
Opioids
Organic synthesis
Continuous flow synthesis
description Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, “slug-flow” regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.
publishDate 2023
dc.date.none.fl_str_mv 2023-06-22
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/213470
10.1590/s2175-97902023e22764
url https://www.revistas.usp.br/bjps/article/view/213470
identifier_str_mv 10.1590/s2175-97902023e22764
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/213470/195518
dc.rights.driver.fl_str_mv Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023)
Brazilian Journal of Pharmaceutical Sciences; v. 59 (2023)
Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023)
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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