Can a Simple Surrogate Model System Be Used to Develop a Continuous Flow Packed Bed Hydrogenation for a Complex Molecule?

Organic Process Research & Development, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Catalytic hydrogenations are key processes in the fine chemical and pharmaceutical industries, but development of such is challenging due to aspects as catalyst deactivation, metal leaching, mass transfer limitations, solubility issues, formation side products. Processes particularly difficult develop when a substrate large molecule containing multiple functional groups. These difficulties significant obstacles for identification robust operating conditions; thus, workflows necessary speed up timelines. The use more cost-effective commercially available surrogate an alternative strategy find optimized conditions, which can then be subsequently validated on real only at later stage development. approach we apply herein designed less compound while minimizing perceived risk failure transferring conditions complex molecule. In this article, our workflow catalytic hydrogenolysis glycopeptide molecule, Cbz-protected (Cbz-GP), packed bed reactor. As part workflow, robustness screening approach, introduced by Collins Glorius, show that lysine (Cbz-Lys), presence additives mimic secondary groups present Cbz-GP or represent residual impurities generated upstream synthesis Cbz-GP. data Cbz-Lys enabled successful deprotection after minor modification. Gratifyingly, few additional experiments were using GP modify achieve >95% conversion under mild within <10 s contact time stable performance over >6 h operation time.

Язык: Английский

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Engineering principles for self-driving laboratories

Nature Chemical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

Язык: Английский

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Simultaneous reaction- and analytical model building using dynamic flow experiments to accelerate process development

Chemical Science, Год журнала: 2024, Номер 15(31), С. 12523 - 12533

Опубликована: Янв. 1, 2024

In modern pharmaceutical research, the demand for expeditious development of synthetic routes to active ingredients (APIs) has led a paradigm shift towards data-rich process development. Conventional methodologies encompass prolonged timelines both reaction model and analytical models. The methods are often separated into different departments can require an iterative optimization process. Addressing this issue, we introduce innovative dual modeling approach, combining Process Analytical Technology (PAT) strategy with optimization. This integrated approach is exemplified in diverse amidation reactions synthesis API benznidazole. platform, characterized by high degree automation minimal operator involvement, achieves PAT calibration through "standard addition" approach. Dynamic experiments executed screen broad space gather data fitting kinetic parameters. Employing open-source software program facilitates rapid parameter additional

Язык: Английский

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Continuous flow synthesis of the antiviral drug tecovirimat and related sp³-rich scaffolds

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Fast, high-yielding syntheses of a medicinally relevant sp 3 -rich polycyclic scaffold have been developed and its synthetic utility demonstrated in range condensation reactions.

Язык: Английский

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Dynamic flow experiments for Bayesian optimization of a single process objective

Reaction Chemistry & Engineering, Год журнала: 2024, Номер 10(3), С. 656 - 666

Опубликована: Дек. 11, 2024

DynO guides an experimental optimization campaign by suggesting the conditions to use in dynamic flow experiments. is supported a Gaussian process and stopping criteria, efficiently combining experiments Bayesian optimization.

Язык: Английский

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