Design of Experiments (DoE) sounds familiar to all process chemists. In GalChimia we apply DoE principles to both process development and drug discovery projects in order to improve critical reactions.
Case study based on the collaboration with a generic company, the objective was to improve the parameter of a specific reaction.
· Generic API producer in Spain.
· Catalytic hydrogenation of a halonitroheterocycle gave an impure amine product (about 60% yield in 24 h, bad impurity profile).
· Optimization following DoE principles in two stages.
- Screening of discrete variables = 14 catalysts.
- Two-level factorial design to optimize concentration, temperature and pressure.
· Yield improved in 25 g scale to 98.8% yield in 6 h, impurities < 0.1%.
· Report & samples sent to client within 2 months.
· Poor solubility & instability issues solved.