Mostrar el registro sencillo del ítem
dc.contributor.author
Paolo, Luciano
dc.contributor.author
Martínez Fornaso, Patricio
dc.contributor.author
Elhalem, Eleonora
dc.contributor.author
Comin, Maria Julieta
dc.contributor.author
Gandolfi Donadío, Lucía
dc.contributor.author
Bellomo, Ana
dc.date.available
2024-11-04T12:04:52Z
dc.date.issued
2024-08
dc.identifier.citation
Paolo, Luciano; Martínez Fornaso, Patricio; Elhalem, Eleonora; Comin, Maria Julieta; Gandolfi Donadío, Lucía; et al.; High‐Throughput Experimentation (HTE) Applied to the Synthesis of API Impurities: A Case Study in Oxidative Decarboxylation of Aryl Acetic Acids; Wiley VCH Verlag; European Journal of Organic Chemistry; 8-2024; 1-7
dc.identifier.issn
1434-193X
dc.identifier.uri
http://hdl.handle.net/11336/247175
dc.description.abstract
High-throughput experimentation (HTE) has dramatically impacted experimental reaction development by enabling the rapid exploration of a diverse set of reaction conditions. During the past few decades, HTE has evolved as a tool to expedite reaction discovery and optimization. This work details the application of HTE to synthesize impurities of active pharmaceutical ingredients (APIs) with ketone/aldehyde functionality, specially focusing on ibuprofen impurity E. Initial experiments using K2S2O8 as oxidant yielded moderate results. Subsequent HTE screens identified cerium ammonium nitrate (CAN) and RuCl3-NaIO4 as new effective decarboxylative oxidants, with RuCl3-NaIO4 in the presence of tetrabutylammonium bromide (TBAB) achieving the highest yield of 65%. This optimized method was successfully applied to synthesize ibuprofen impurity E on a gram scale. Additionally, the applicability of these methods to obtain other API related substances, such as naproxen impurity L and ketoprofen impurity A, was demonstrated. This research highlights the potential of HTE to streamline the synthesis of API impurities, making them widely accessible for pharmaceutical development purposes.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley VCH Verlag
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
API IMPURITIES
dc.subject
HTE
dc.subject
OPTIMIZATION
dc.subject.classification
Química Orgánica
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
High‐Throughput Experimentation (HTE) Applied to the Synthesis of API Impurities: A Case Study in Oxidative Decarboxylation of Aryl Acetic Acids
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-10-24T18:00:31Z
dc.journal.pagination
1-7
dc.journal.pais
Alemania
dc.description.fil
Fil: Paolo, Luciano. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina
dc.description.fil
Fil: Martínez Fornaso, Patricio. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina
dc.description.fil
Fil: Elhalem, Eleonora. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Comin, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina
dc.description.fil
Fil: Gandolfi Donadío, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina
dc.description.fil
Fil: Bellomo, Ana. Instituto Nacional de Tecnología Industrial. Centro de Investigación y Desarrollo en Química; Argentina
dc.journal.title
European Journal of Organic Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202400720
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/ejoc.202400720
Archivos asociados