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dc.contributor.author
Paolo, Luciano  
dc.contributor.author
Martínez Fornaso, Patricio  
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Elhalem, Eleonora  
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Comin, Maria Julieta  
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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  
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HTE  
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OPTIMIZATION  
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Química Orgánica  
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Ciencias Químicas  
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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