Scalable Quasi-Divided Cell Operation Using Spinning Cylinder Electrode Technology: Multigram Electrochemical Synthesis of an Axitinib Intermediate

Abstract

Electrochemical synthesis of a key thiol intermediate in the preparation of axitinib has been achieved on a multi-10 g scale using a modified spinning cylinder electrode reactor adapted for "quasi-divided" cell operation. This concept enables the target cathodic reduction to occur without the need for sacrificial electrodes or divided cells equipped with ion exchange membranes. The new reactor design, based on a scalable platform, features an inner spinning cathode made of leaded bronze and a reactor vessel to which a variable number of counter-electrode rods can be attached. This setup permits high flexibility in the cathode/anode surface area ratio required for "quasi-divided" cell operation. The setup has been shown to provide excellent yields for the target thiol intermediate in batch and flow recirculation modes. Continuous operation using a cascade of three reactors was also demonstrated.

Design of Experiments-Based Optimization of an Electrochemical Decarboxylative Alkylation Using a Spinning Cylinder Electrode Reactor

“…The center points for the current density and the amount of charge were based on small-scale experiments (6.6 mA/cm 2 and 4 F/mol, respectively). For the electrode spinning speed and pump flow rate, the selected center points were based on previous experience with the system. , …”

“…However, due to the narrow interelectrode gap and static nature of the electrodes, the presence of solids can easily cause clogging of the reactor and electrode fouling. We have recently developed a scalable electrolysis cell that overcomes the main drawbacks of parallel-plate flow reactors, including the processing of solid suspensions. , The cell features a moving cylindrical electrode, which spins around its axis and is concentrically inserted into a static pipe-shaped counter electrode . The spinning cylinder electrode diameter is 10 mm narrower than the static counter electrode, providing an interelectrode gap of 5 mm.…”