Artículo
High‐Throughput Experimentation (HTE) Applied to the Synthesis of API Impurities: A Case Study in Oxidative Decarboxylation of Aryl Acetic Acids
Paolo, Luciano; Martínez Fornaso, Patricio; Elhalem, Eleonora
; Comin, Maria Julieta
; Gandolfi Donadío, Lucía
; Bellomo, Ana
Fecha de publicación:
08/2024
Editorial:
Wiley VCH Verlag
Revista:
European Journal of Organic Chemistry
ISSN:
1434-193X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
API IMPURITIES
,
HTE
,
OPTIMIZATION
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
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
Compartir
Altmétricas