Flow chemistry is an evolving technology that shows great potential for improving the efficiency and safety of synthetic chemistry reactions. The fundamental concept of flow chemistry is carrying out chemistry in a continuous stream through a small diameter tube, instead of conducting reactions in a vessel also known as batch chemistry. With the chemistry occurring in small diameter tubes, the surface area to mass ratio allows for efficient heat transfer, facilitating exquisite control of reaction temperature, and affording the safe use of thermally unstable or reactive reagents or intermediates. This process also offers other advantages over batch chemistry, such as the capability for automation, safer high temperature and pressure reactions, and precise control of stoichiometry. Lastly, flow chemistry can facilitate consistency during scale-up, given that a flow reaction conducted on a 10 mg scale is conducted in the same manner as a 10 kg scale, with the difference being the length of time required to pass reagents through the reactor.Herein, we describe a multigram (>350 g) deoxyfluorination reaction of a primary alcohol in support of advanced in-vivo studies. A commercial segmented flow reactor, capable of automation was utilized to quickly optimize conditions by evaluating several reagents against reaction conditions (time, temperature, solvent, and stoichiometry). The elucidated conditions were safely brought to the multigram scale using a commercial continuous flow reactor, improving the overall step from 35% to 79%. 

Fluorination in flow: Safe and expedient scale-up of deoxyfluorination reactions using flow chemistry

246th National Meeting (2013)

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