Case studies in process screening and optimization utilizing a new automated reactor-analysis system

The application of a new automated workstation for conducting solution-phas e reactions in parallel during chemical process development is described. T he fully automated reactor-analysis system is capable of reagent/reactant a ddition, temperature and agitation control, and sample extraction/quench/in jection for online HPLC analysis. Both precision and accuracy of the fluidi c delivery and sampling systems were measured through the use of standard u ltraviolet chromophore solutions in conjunction with HPLC analysis. Agitati on efficiency was evaluated using a phase-transfer catalysis reaction known to be rate-dependent on stirring frequency. Chemistry cases examined inclu ded several single and multistep reactions studied to identify the best rea gent/solvent combinations (screening) and optimal levels of continuous vari ables such as temperature, concentration, and stoichiometry (optimization), A multistep route to a chiral substituted imidazolidin-2-one was developed from initial route scouting through reaction condition screening, optimiza tion, and scale-up. Reactions performed included alkylation, reduction, oxi dation, reductive amination, displacement, and cyclization.