Scalable Subsecond Synthesis of Drug Scaffolds via Aryllithium Intermediates by Numbered-up 3D-Printed Metal Microreactors.
ACS Cent Sci
; 8(1): 43-50, 2022 Jan 26.
Article
em En
| MEDLINE
| ID: mdl-35106371
ABSTRACT
Continuous-flow microreactors enable ultrafast chemistry; however, their small capacity restricts industrial-level productivity of pharmaceutical compounds. In this work, scale-up subsecond synthesis of drug scaffolds was achieved via a 16 numbered-up printed metal microreactor (16N-PMR) assembly to render high productivity up to 20 g for 10 min operation. Initially, ultrafast synthetic chemistry of unstable lithiated intermediates in the halogen-lithium exchange reactions of three aryl halides and subsequent reactions with diverse electrophiles were carried out using a single microreactor (SMR). Larger production of the ultrafast synthesis was achieved by devising a monolithic module of 4 numbered-up 3D-printed metal microreactor (4N-PMR) that was integrated by laminating four SMRs and four bifurcation flow distributors in a compact manner. Eventually, the 16N-PMR system for the scalable subsecond synthesis of three drug scaffolds was assembled by stacking four monolithic modules of 4N-PMRs.
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MEDLINE
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En
Revista:
ACS Cent Sci
Ano de publicação:
2022
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Article