Process Intensive Synthesis of Propofol Enabled by Continuous Flow Chemistry

• Laurent Vinet^a
• Lorenzo Di Marco^a
• Vanessa Kairouz^a
• André B. Charette^a

• ^aCentre in Green Chemistry and Catalysis, Center for Continuous Flow Synthesis, Department of Chemistry, Université de Montréal, 1375, av. Thérèse Lavoie-Roux, Montréal, Québec H2V 0B3, Canada

A multi-step process using continuous flow chemistry to produce propofol is described. A scale-up of a 5-stage process (two continuous flow chemical steps, two extractions using a semi-batch approach, and one purification) provided propofol in high purity. This process minimizes the number of impurities formed during the double Friedel–Crafts reaction allowing to run two continuous flow chemical steps sequentially. The use of simple, inexpensive, and readily available reagents affords a viable process for this widely employed active pharmaceutical ingredient.

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