(621e) Data-Rich Reaction Profiling of Copper-Catalyzed Methoxylation of an Aryl Halide

In the development and scale-up of viable synthetic pathways for active pharmaceutical ingredients (API’s), it is advantageous to understand a reaction’s sensitivities to various process conditions. Reaction profiling is a useful way to characterize these sensitivities but can be very time, labor, and resource intensive. The use of small volume parallel reactors with automated sampling strategies enables data rich experimentation in a resource-sparing manner. Inclusion of in-situ analytical techniques, such as FTIR, provides further insight to the reaction dynamics. This data can provide mechanistic insight to the reaction and can be used to develop a robust kinetic model of the reaction.

We employ this approach in a case study of the copper-catalyzed methoxylation of an aryl halide. The resulting profiles were used to construct a kinetic model in agreement with a proposed reaction mechanism. Laboratory profiling results were also used as a comparison to those obtained in the pilot plant during scale-up.