Solvent switching in continuous multi-step chemo-enzymatic synthesis: chiral amino pyridine derivatives as a case study
Lehmann, Hansjoerg, Snajdrova, Radka, Paradisi, Francesca, Diaz-Kruik, Pablo, Padrosa, David Roura and Hegarty, Eimear (2024) Solvent switching in continuous multi-step chemo-enzymatic synthesis: chiral amino pyridine derivatives as a case study. Organic process research & development. ISSN 1520-586X; 1083-6160
Abstract
Chiral α-(hetero)aryl primary amines are gaining momentum for their biological activities and their use as building blocks in more complex molecules. Here we report the synthesis of a 2-acetyl-6-pyridine derivative through a continuous chemoenzymatic strategy enabled throughout by careful solvent selection and phase switching. Combining a first biocatalytic transamination reaction performed by TsRTA in a biphasic system in continuous flow, with in line Boc-protection and Suzuki coupling of a boronic acid, we achieved the final product in a >99% conversion. This strategy not only constitues an important example of chemoenzymatic combinations in continuous flow, but highlights the importance of the reaction design to minimize waste (through unreacted substrate recirculation), avoid time intensive workups (through inline extractions) and achieve the product in excellent enantiomeric excess (99% e.e. and 68 mg/L·h)
Item Type: | Article |
---|---|
Date Deposited: | 06 Aug 2024 00:46 |
Last Modified: | 06 Aug 2024 00:46 |
URI: | https://oak.novartis.com/id/eprint/52771 |