Multi-platform synthesis of ondansetron featuring process intensification in flow

Hato, Yoshio; Jamison, Timothy F.

doi:10.1039/d3re00249g

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…5 Extensive research has been conducted on the flow synthesis of APIs, including ibuprofen (a widely used painkiller), 11,12 artemisinin (an antimalaria drug), 13 olanzapine (an atypical antipsychotic), 14 efavirenz (a drug against the human immunodeficiency virus), 15 and rolipram (an anti-inflammatory drug). 16 More recent examples are lomustine (a drug for treatment of brain tumors), 17 dolutegravir (an anti-HIV drug), 18 ondanse-tron (a drug to prevent nausea and vomiting caused by cancer chemotherapy), 19 and a bioactive fragment of salbutamol (an asthma medication). 20 Given the limited time available for process design in the pharmaceutical industry, 21 a modeling and simulation approach can be advantageous.…”

Section: ■ Introductionmentioning

confidence: 99%

Hybrid Modeling of an Active Pharmaceutical Ingredient Flow Synthesis in a Ring-Opening Reaction of an Epoxide with a Grignard Reagent

Kim,

Hayashi,

Badr

et al. 2023

Ind. Eng. Chem. Res.

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This work presents hybrid modeling of an active pharmaceutical ingredient flow synthesis in a ring-opening reaction of an epoxide with a Grignard reagent. Conducting this reaction in a batch reactor is challenging due to its fast and highly exothermic nature, which makes it difficult to collect kinetic data. To address this, a flow experiment was conducted with varying parameters, such as the inner diameter and temperature, to collect kinetic information. A onedimensional flow mechanistic model was then developed, and two reaction mechanisms were assessed, with the Swain and Boyles mechanism found to show better results than the Meisenheimer and Casper mechanism. In this model, the impact of changes in reactor inner diameters was considered by adjusting the preexponential factor as a function of the varying Reynolds number, which simplifies the effort needed to consider the inner diameter effects relative to the development of two-dimensional models. The reaction presents a further difficulty due to the generation of impurities, and the underlying mechanism is still unclear. To tackle this challenge, a data-driven approach, a random forest regression model, was adopted to quantify them. The adoption of the data-driven part enabled the quantification of the impurity with high accuracy, demonstrating the potential strength of this approach when not all reaction mechanisms are fully understood. Overall, the hybrid model approach allowed for a deeper understanding of the reaction and improved the ability to predict its behavior.

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Section: ■ Introductionmentioning

confidence: 99%

Hybrid Modeling of an Active Pharmaceutical Ingredient Flow Synthesis in a Ring-Opening Reaction of an Epoxide with a Grignard Reagent

Kim,

Hayashi,

Badr

et al. 2023

Ind. Eng. Chem. Res.

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A green and efficient monoacylation strategy for symmetrical diamines in microreactors

Xu,

Liu,

et al. 2024

React. Chem. Eng.

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Multi-platform synthesis of ondansetron featuring process intensification in flow

Abstract: The synthetic studies of ondansetron by a multi-platform, built-for-purpose approach were presented. The studies highlighted the complementary strengths of batch and flow approaches to API synthesis.

Cited by 2 publications

References 30 publications

Hybrid Modeling of an Active Pharmaceutical Ingredient Flow Synthesis in a Ring-Opening Reaction of an Epoxide with a Grignard Reagent

Hybrid Modeling of an Active Pharmaceutical Ingredient Flow Synthesis in a Ring-Opening Reaction of an Epoxide with a Grignard Reagent

A green and efficient monoacylation strategy for symmetrical diamines in microreactors

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