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A recently described C(sp3)–H activation reaction to synthesise aziridines was used as a model reaction to demonstrate the methodology of developing a process model using model-based design of experiments (MBDoE) and self-optimisation approaches in flow. The two approaches are compared in terms of experimental efficiency. The self-optimisation approach required the least number of experiments to reach the specified objectives of cost and product yield, whereas the MBDoE approach enabled a rapid generation of a process model.