Scaled up and telescoped synthesis of propofol under continuous-flow conditions.
MARTINS , Guilherme M.; MAGALHÃES, Maria F. A.; BROCKSOM, Timothy J.; BAGNATO, Vanderlei Salvador; OLIVEIRA, Kleber Thiago de.
MARTINS , Guilherme M.; MAGALHÃES, Maria F. A.; BROCKSOM, Timothy J.; BAGNATO, Vanderlei Salvador; OLIVEIRA, Kleber Thiago de.
Abstract: Herein we report a machine-assisted and scaled-up synthesis of propofol, a short-acting drug used in procedural sedation, which is extensively in demand during this COVID-19 pandemic. The continuous-flow protocol proved to be efficient, with great potential for industrial translation, reaching a production up to 71.6 g per day with process intensification (24 h-continuous experiments). We have successfully telescoped a continuous flow approach obtaining 5.74 g of propofol with productivity of 23.0 g/day (6 h-continuous experiment), proving the robustness of the method in both separated and telescoped modes. Substantial progress was also achieved for the in-line workup, which provides greater safety and less waste, also relevant for industrial application. Overall, the synthetic strategy is based on the Friedel-Crafts di-isopropylation of low-cost phydroxybenzoic acid, followed by a decarboxylation reaction, giving propofol in up to 84% overall yield and very low by-product formation.
@article={003094610,author = {MARTINS , Guilherme M.; MAGALHÃES, Maria F. A.; BROCKSOM, Timothy J.; BAGNATO, Vanderlei Salvador; OLIVEIRA, Kleber Thiago de.},title={Scaled up and telescoped synthesis of propofol under continuous-flow conditions},journal={Journal of Flow Chemistry},note={v. 12, n. 3, p. 371-379},year={2022}}