*2.2. Experimental Setup*

All separation experiments were performed in the setup shown in Figure 3. The plant consisted of two tubular crystallizers (C1 and C2, Figure 3) with an individual volume of approximately 0.5 L and a total height of 1130 mm. Each double-jacketed tubular crystallizer was composed of a conical section in the lower part and a cylindrical section in the upper part of the columns. Thus, the fluid velocity of a liquid phase passing through the crystallizers changes with the height of the columns due to the increasing diameter in the conical section. At the transition between the upper and lower section, where the diameter is the largest, the fluid velocity becomes constant again over the height of the cylindrical part.

**Figure 3.** Process scheme with the main components of the utilized continuous fluidized bed plant.

The temperature inside the columns was measured at the inlet, in the middle, and at the outlet via resistance thermometers (Pt100s). Temperature control was ensured by two thermostats connected to the respective middle Pt100s. In this study, the middle temperature is referred to as the crystallization temperature for the sake of simplicity, even though a temperature gradient will be present over the height of the columns due to the fluid flow.

Both crystallizers were coupled via heated steel pipes and flexible heated hoses with a double-jacketed feed tank on the scale of 7.5 L. A propeller-type stirrer was utilized in this tank during the separation experiments to suspend a certain excess mass of racemic solid phase in a solution saturated at a defined initial temperature. This excess of solid phase served to re-saturate the depleted mother liquors from the crystallizers during the process to ensure constant initial conditions at the inlet of the columns. The temperature within the feed tank was again measured by a Pt100 and controlled by a thermostat.

Clear saturated racemic solution was withdrawn during the process from the feed tank via glass filters and was pumped continuously from the bottom through the tubular crystallizers using gear pumps. The rotation speed of these gear pumps was controlled by Coriolis mass flowmeters to ensure a constant volumetric flowrate.

To harvest the product, each column had a product outlet at a height of 365 mm, close to the end of the conical section. The product removal was realized periodically due to the scale of the plant, using solenoid valves, which were controlled by photoelectric barriers as described in the next section.

Due to the mild mixing conditions of the particulate phase, secondary nucleation will not be sufficient to counterbalance the loss of crystals of the periodically continuous product removal. Hence, a continuous seeding strategy was necessary, which also supports Preferential Crystallization by providing enantiopure crystals. Thus, the largest particles present at the bottom of the crystallizer columns were withdrawn via peristaltic pumps into a bypass. They were pumped, subsequently, through high-speed dispersers, which were utilized as mills working on the rotor-stator principle. Afterward, the ground crystals were fed back as seed material to the process.
