Application note: Enhancing reaction understanding with online NMR reaction monitoring – application to chemical route development

In this work, we demonstrate the complementarity of NMR and infrared (IR) spectroscopy and show the use of NMR to improve the understanding and robustness of the synthesis of an active pharmaceutical ingredient (API) precursor…

The quantitative nature of nuclear magnetic resonance (NMR) and the fact that it is structurally rich and non-intrusive makes the technique extremely powerful for the identification and characterisation of reaction intermediates, providing insights into the reaction mechanisms and kinetics of chemical reactions.

While many chemical transformations have been analysed in standard NMR tubes over the years, physical and chemical restrictions limit the types of reactions to which this form of NMR reaction monitoring is applicable. The lack of control over parameters such as mixing, temperature and pressure can have significant effects on the rate of a reaction. It has been demonstrated that the use of online reaction monitoring circumvents these limitations.

In this work, we demonstrate the complementarity of NMR and infrared (IR) spectroscopy and show the use of NMR to improve the understanding and robustness of the synthesis of an active pharmaceutical ingredient (API) precursor.