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Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

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Published on: November 15, 2017

Continuous Flow Synthesis of Propofol.

Romain Mougeot¹, Philippe Jubault¹, Julien Legros¹

¹CNRS, INSA Rouen, UNIROUEN, Normandie University, COBRA, 76000 Rouen, France.

Molecules (Basel, Switzerland)

|December 10, 2021

Summary

We developed a continuous flow process for synthesizing Propofol, an essential anesthetic. This efficient method simplifies the production of this widely used intravenous drug.

Keywords:

Friedel–Crafts active pharmaceutical ingredient anesthetics decarboxylation

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Area of Science:

Chemical Engineering
Organic Synthesis
Medicinal Chemistry

Background:

Propofol (2,6-diisopropylphenol) is a critical short-acting intravenous anesthetic.
It is widely utilized in intensive care units for sedation and hypnosis.
Current synthesis methods may not be optimized for efficiency and scalability.

Purpose of the Study:

To develop and report a continuous flow process for the synthesis of Propofol.
To optimize the production of 2,6-diisopropylphenol using flow chemistry.
To provide an efficient and scalable method for anesthetic synthesis.

Main Methods:

A two-step synthesis procedure was employed.
The process involved a double Friedel-Crafts alkylation under continuous flow.
A subsequent decarboxylation step was also performed in continuous flow.

Main Results:

A continuous flow process for 2,6-diisopropylphenol synthesis was successfully established.
The two-step procedure, including Friedel-Crafts alkylation and decarboxylation, was optimized for flow conditions.
This method offers a streamlined approach to Propofol production.

Conclusions:

Continuous flow chemistry provides an effective platform for Propofol synthesis.
The reported process offers potential for improved efficiency and scalability in anesthetic manufacturing.
This work contributes to the advancement of flow chemistry applications in pharmaceutical synthesis.