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放大合成，丙泊酚是一种用于程序镇静的短效药物，在本次 COVID-19 大流行期间需求量很大。事实证明，连续流方案是高效的，具有巨大的工业转化潜力，通过工艺强化（24 小时连续实验），产量可达每天 71.6 克。我们成功地采用连续流方法进行伸缩，获得了 5.74 克异丙酚，生产率为 23.0 克/天（连续实验 6 小时），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，提供了更高的安全性和更少的废物，也与工业应用相关。总体而言，该合成策略基于低成本对羟基苯甲酸的弗里德尔-克来福特二异丙基化，然后进行脱羧反应，以高达 84% 的总收率和非常低的副产物形成得到异丙酚。