A Continuous Flow Sulfuryl Chloride Based Reaction – Synthesis of a Key Intermediate in a New Route Toward Emtricitabine and Lamivudine
- Juliana M. de Souza
- Mateo Berton
- David R. Snead*
- D. Tyler McQuade
- Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, 23284-3068, USA.Read the publication that featured this abstract
We demonstrate a continuous two-step sequence where a sulfenyl chloride is formed, trapped by vinyl acetate and chlorinated further via a Pummerer rearrangement. This sequence produces a key intermediate in our new approach to the oxathiolane core used to prepare the anti-retroviral medicines Emtricitabine and Lamivudine. During batch scale-up to tens of grams, we found that the sequence featured a strong exotherm, temperature and pressure sensitivity, and evolution of hydrogen chloride and sulfur dioxide. 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 141g/h throughput system.
The Vapourtec R-Series is, quite simply, unrivalled for flow chemistry
- Flexible :
- Precise :
The R-Series is undoubtedly the most versatile, modular flow chemistry system available today.
The Vapourtec E-Series is the perfect introductory system for flow chemistry
- Robust :
- Easy to use :
The E-Series is a robust and affordable, entry level flow chemistry system designed for reliability and ease of use.