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DOI: 10.1055/a-1664-2282
Rapid Multigram-Scale End-to-End Continuous-Flow Synthesis of Sulfonylurea Antidiabetes Drugs: Gliclazide, Chlorpropamide, and Tolbutamide
We thank the National Research Fund (NRF SARChI Grant) and Technology Innovation Agency (TIA) for financial support.
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Abstract
A multigram-scale robust, efficient, and safe end-to-end continuous-flow process for the diabetes sulfonylurea drugs gliclazide, chlorpropamide, and tolbutamide is reported. The drugs were prepared by the treatment of an amine with a haloformate affording carbamate, which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was obtained in 87% yield within 2.5 minutes total residence time with 26 g/h throughput; 0.2 kg of the drug was produced in 8 hours of running the system continuously. Chlorpropamide and tolbutamide were both obtained in 94% yield within 1 minute residence time with 184–188 g/h throughput; 1.4–1.5 kg of the drugs was produced in 8 hours of running the system continuously. N-Substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.
Key words
chlorpropamide - gliclazide - diabetes - end-to-end continuous flow - sulfonylurea - and tolbutamideSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1664-2282.
- Supporting Information
Publication History
Received: 16 September 2021
Accepted after revision: 07 October 2021
Accepted Manuscript online:
07 October 2021
Article published online:
22 November 2021
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