(287d) Surprisingly Complex Phase Behavior of 3,5,5-Trimethylpyrrolidin-2-One Affecting Its Chiral Puirty Enrichment through Crystallization
AIChE Annual Meeting
2019 AIChE Annual Meeting
PAT and Process Monitoring in Crystallization Development and Manufacturing
Tuesday, November 12, 2019 - 9:06am to 9:27am
The separation of enantiomers is of great interest to the pharmaceutical industry. One of the tools utilized for the production of a pure chiral active phamaceutical ingredient (API) is enrichment of enantiomers by crystallization. Resolution of a chiral compound strongly depends on the kind of solid state crystal lattcie that it forms. Three common types of racemates include racemic compound, conglomerate and solid solution.
In this work, thorough solid state characterizations of (S)-3,5,5-trimethylpyrrolidin-2-one is presented. While macro-scale composition of the solution phase and the solid phase suggested a simple racemic solid solution, the detailed crystal structure of the solid phase proved to be much more complex. Multiple solid phases exist; however, the system still seems to be on a solid solution continuum.
Based on the phase diagram, the yield and chiral purity trade-off was established to guide the optimization of crystallization process. It is also found the yield and chiral purity relationship at equilibrium remains the same in different solvent systems.