Flash chemistry approach to organometallic C-glycosylation for the synthesis of remdesivir

In a rapidly changing environment, such as the current COVID-19 pandemic, continuous flow reactors bear the potential to increase the production of urgently needed active pharmaceutical ingredients (APIs) on demand In the synthesis of remdesivir, the organometallic C-glycosylation step was identified as a limitation for the large-scale production, requiring long addition periods and cryogenic temperatures Previous studies have focused on a Grignard-based protocol, but a flash chemistry approach, using organolithium reagents, has facilitated significant improvements After gaining further understanding of the C-glycosylation, this step was successfully transferred to a five-stream continuous flow process, achieving 60% yield at a moderate temperature (−30 °C) in a total residence time of just 8 s Stable processing was demonstrated for 2 h, providing an exceptionally high space−time yield of 10 4 kg L−1 h−1, in a scalable flow reactor system © XXXX American Chemical Society