A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine
| Autor: | Mateo Berton, D. Tyler McQuade, David R. Snead, Juliana M. de Souza |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
scale-up
Sulfenyl chloride flow chemistry Pummerer rearrangement Communication Organic Chemistry Sulfuryl chloride Flow chemistry Combinatorial chemistry chemistry.chemical_compound chemistry Reagent API Vinyl acetate lamivudine Physical and Theoretical Chemistry Hydrogen chloride Sulfur dioxide emtricitabine continuous processing |
| Zdroj: | Organic Process Research & Development |
| ISSN: | 1520-586X 1083-6160 |
| Popis: | We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines emtricitabine and lamivudine. During batch scale-up to tens of grams, we found that the sequence featured a strong exotherm and evolution of hydrogen chloride and sulfur dioxide. Keeping gaseous byproducts in solution and controlling the temperature led to better outcomes. These reactions are ideal candidates for implementation in a continuous mesoscale system for the sake of superior control. In addition, we found that fast reagent additions at controlled temperatures decreased byproduct formation. Herein we discuss the flow implementation and the final reactor design that led to a system with a 141 g/h throughput. |
| Databáze: | OpenAIRE |
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