Continuous Ozonolysis as a Key Step of the Darunavir Synthesis Using the IceCube™ Flow Reactor

AIDS is one of the most threatening diseases spread across the planet, affecting about 35 million people worldwide. To improve the quality of life of those affected by HIV, a number of antivirals were developed, such as Darunavir. This molecule has a complex bicyclic core, the synthesis of which is well documented in the literature.

State of the art: An approach described by Ghosh and his co-workers includes an ozonolysis step, which is performed under batch conditions resulting in the desired ketone with 98% yield after 3 hours.[6,7] However, handling the gaseous ozone and working at a very low temperature (78°C) is inconvenient. Adapting the synthesis to a continuous flow system
provides a safe and rapid alternative solution by using in-situ generated ozone, a closed system, and higher temperatures. In this application note, we demonstrate that continuous flow ozonolysis can easily be carried out utilizing the IceCube™ Flow Reactor, developed by ThalesNano, in a safe and efficient way.