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 p-hydroxybenzoic acid, followed by a decarboxylation reaction, giving propofol in up to 84% overall yield and very low by-product formation.

在此，我们报告了丙泊酚的机器辅助和放大合成，丙泊酚是一种用于程序镇静的短效药物，在 COVID-19 大流行期间广泛需求。连续流协议被证明是有效的，具有巨大的工业转化潜力，通过过程强化（24 小时连续实验）达到每天 71.6 克的产量。我们已经成功地对连续流动方法进行了伸缩，获得了 5.74 g 丙泊酚，生产率为 23.0 g/天（6 小时连续实验），证明了该方法在分离模式和伸缩模式下的稳健性。在线后处理也取得了实质性进展，它提供了更高的安全性和更少的浪费，这也与工业应用相关。总体而言，合成策略是基于低成本的傅克二异丙基化对羟基苯甲酸，然后进行脱羧反应，得到丙泊酚，总收率高达 84%，副产物形成率非常低。