New paper out in Communications Chemistry: Clonidine, an API that hasn’t changed since the 1960s, now made in 24 minutes instead of 18 hours.
Clonidine is used for hypertension, ADHD, and opioid withdrawal. The published routes go through thiophosgene, run for more than 18 hours in batch, and have seen essentially no modernization in sixty years.
Working with the team at CSIR, Chimie ParisTech and Diverchim, the synthesis now runs in continuous flow: five transformations, 24 minutes total residence time, 54% overall yield, and no thiophosgene.
The closest batch precedent in the literature, on a close analogue, ran 18 hours at 150 °C and gave 7%.
In flow, at the same temperature with 5 minutes residence time, the ring closure gave 87%.
Not a better catalyst - just not leaving the molecule in the heat long enough to decompose.
Bayesian optimization did the condition finding across the earlier steps, typically in 9 to 14 experiments each.
View the full paper here: https://www.nature.com/articles/s42004-026-02096-2
