Isothermal suspension conversion as a route to cocrystal production: One-pot scalable synthesis

Isothermal suspension conversion is presented as a suitable method for the manufacture of pure cocrystal products once the ternary phase diagram (TPD) for the cocrystal system in the desired solvent is available. One:one and 3:2 cocrystals of p-toluenesulphonamide/triphenylphosphine oxide were produced in acetonitrile and dichloromethane using this method. Eight individual batches of product were prepared with complete conversion to pure product achieved in seven batches. Product recovery (77-99%), reaction conversion (17-89%), and volumetric productivity (0.03-0.63 g/cm³) were calculated for each product batch. These parameters are essentially determined by the batch operating mass fraction composition selected from the TPD, allowing for tailoring of processing conditions to suit process requirements and capabilities by careful selection of the optimum operating mass fraction composition.