Phase transfer catalysis of N-alkylation of a lysergic acid derivative in microfluidic systems

In the Research Group of Microreactors, we have developed a new method for preparing a compound derived from ergot, which is used in the production of nicergoline, a drug for the treatment of dementia and Alzheimer’s disease. The reaction takes place in a two-phase immiscible liquid system using phase transfer catalysis (PTC). Ultrasound was used to accelerate the process, improving mixing and mass transfer between the liquids. Four different flow reactor configurations were tested, including microchip and capillary systems, some of which were sonicated throughout their entire volume. The optimized method achieved high selectivity (95%) and a production rate of up to 23 g/h in a reactor with a volume of only 3 ml. It was also shown that the use of ultrasound can double the yield per unit volume of the reactor without compromising the efficiency of the reaction or the purity of the product. These results confirm that flow synthesis using microfluidic devices in combination with ultrasound can significantly improve the preparation of pharmaceutically important substances.

• Jaklova N., Stavarek P., Vychodilova H., Malikova S., Kluson P., Holas T.: Phase transfer catalysis of N-alkylation of a lysergic acid derivative in microfluidic systems. Eng. J. 2025, 523 (1 Nov 2025) 167999. doi.org/10.1016/j.cej.2025.167999