Academic Journal
Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis
| العنوان: | Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis |
|---|---|
| المؤلفون: | Clayton, AD, Pyzer-Knapp, E, Purdie, M, Jones, M, Barthelme, A, Pavey, J, Kapur, N, Chamberlain, T, Blacker, J, Bourne, R |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | White Rose Research Online (Universities of Leeds, Sheffield & York) |
| الوصف: | The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization-deprotection reaction sequence, used in the synthesis of a precursor for 1-methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in-depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://eprints.whiterose.ac.uk/193147/1/Angew%20Chem%20Int%20Ed%20-%202022%20-%20Clayton%20-%20Bayesian%20Self%E2%80%90Optimization%20for%20Telescoped%20Continuous%20Flow%20Synthesis.pdf; https://eprints.whiterose.ac.uk/193147/7/Angew%20Chem%20Int%20Ed%20-%202022%20-%20Clayton%20-%20Bayesian%20Self%E2%80%90Optimization%20for%20Telescoped%20Continuous%20Flow%20Synthesis.pdf; Clayton, AD orcid.org/0000-0002-4634-8008 , Pyzer-Knapp, E, Purdie, M et al. (7 more authors) (2023) Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis. Angewandte Chemie International Edition, 62 (3). e202214511. ISSN 1433-7851 |
| الاتاحة: | https://eprints.whiterose.ac.uk/193147/ https://eprints.whiterose.ac.uk/193147/1/Angew%20Chem%20Int%20Ed%20-%202022%20-%20Clayton%20-%20Bayesian%20Self%E2%80%90Optimization%20for%20Telescoped%20Continuous%20Flow%20Synthesis.pdf https://eprints.whiterose.ac.uk/193147/7/Angew%20Chem%20Int%20Ed%20-%202022%20-%20Clayton%20-%20Bayesian%20Self%E2%80%90Optimization%20for%20Telescoped%20Continuous%20Flow%20Synthesis.pdf |
| Rights: | cc_by_4 |
| رقم الانضمام: | edsbas.C00D65E3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |