Check out our new publication! This great study has been achieved in a successful collaboration with scientists of EGIS Pharmaceutical PLC.
doi: https://doi.org/10.1007/s41981-019-00036-x
In this study, the piperazine formation step of vortioxetine synthesis was investigated under continuous flow conditions. The batch variant of this step could be carried out at laboratory scale at 130–135 °C with a long reaction time (27 h) followed by a laborious optimization process, but the formation of a significant amount of side-products could be detected, thus an efficient purification procedure was necessary. In the attempted scale-up of the batch reaction, a complete conversion could not at all be reached, even after elongated reaction times (36 h). The continuous-flow experiments were carried out in a new, purpose-built flow system. The examinations were extended to a wide range of reaction parameters (ratio of solvents, concentration and molar ratio of reagents, geometry of coiled loop reactor, residence time, temperature) and to the feasibility study of scale-up. In the second part of the experiments, the fine-tuning of scaled-up reaction parameters of continuous flow synthesis was carried out using a systematic design of experiments approach. Finally 190 °C reaction temperature and 30 min of residence time led to the highest efficacy in the production of vortioxetine drug substance with high yield and purity.
