Continuous processing expands the range of conditions that are easily accessible to the bench chemist. Over the past decade, our group has invested in this technology to recognize its full potential within the context of pharmaceutical manufacturing. This presentation describes the thermal deprotection of <i>tert</i>-butyl esters utilizing a high temperature plug flow reactor (PFR). Initial batch screening is done in small pressure vessels to determine rough time and temperature requirements for flow pilot studies. The PFR is easily constructed from affordable and available materials; high pressure syringe pumps feed material through stainless steel tubing, which is heated in a GC oven. The reactions are typically conducted between 200 and 250 °C with a residence time of 10–30 minutes. These conditions provide a range of carboxylic acid and amino acid products in good yields with high purity. The reaction is conducted in THF or IPA with a small amount of water. Acid or base catalysis is not required, allowing for simplified workup and isolation, especially with regard to highly water soluble amphoteric materials. Comparable yields and reaction profiles are achieved on scales ranging from 500 mg to 20 g.

Catalyst-free thermal deprotection of tert-butyl esters

253rd National Meeting (2017)

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