Establishment of a Simple and Efficient Screening Protocol for Optical Resolution by Diastereomeric Salt Crystallization: Analyzing Success-Related Factors and Constructing Reliable Procedures from Previous Studies

This paper presents a simple and efficient screening protocol for optical resolution by diastereomeric salt crystallization, developed from an analysis of our historical data. Original screening kits have been created utilizing selected commercially available chiral acids and bases, which encompass all reagents that have demonstrated promising results in the diastereomeric salt crystallization of 30 intermediates examined in our laboratories. The influence of various conditions such as crystallization solvents, the equivalents of the resolving agent, additives, and temperature was analyzed to establish clear procedures for the first screening experiments. The advantages of this procedure include its simplicity, accessibility, and high likelihood of success supported by historical achievements, as demonstrated in the optical resolution of the PTDSS1 inhibitor’s intermediate. Overall, this research offers valuable insights into the techniques of diastereomeric salt crystallization and contributes to the efficient acquisition of chiral compounds and advancement of process chemistry.