Shane Grosser discusses how Merck's Process Development Intensification Laboratory develops new tools and methods to increase the speed and decrease the cost of chemical process development.
Innovative Techniques to Synthesize Breakthrough Molecules
Many chemists and engineers are constrained at the bench when exploring a wide range of experimental conditions. Due to inherent shortcomings associated with traditional methods, the ability to discover new synthetic pathways in a timely manner is limited. Reaction temperature is a critical parameter which cannot be investigated with traditional synthesis techniques, and is often not optimized due to time pressures associated with development. When expanding experimental evaluations to other critical process parameters such as dosing rate, stirring, and pH - traditional synthesis techniques lack control capabilities and hinder the pace of development. Furthermore, scientists can feel burdened by the requirements to record key process and performance data electronically and synchronize it with other analytical measurements for historical or regulatory purposes. Traditional equipment to support chemical synthesis, such as heating mantles, ice baths, and cryostats combined with standalone dosing funnels and stirrer motors, have limited temperature range, poor control capabilities, are manually intensive and do not easily capture and report real-time data as the synthesis proceeds.
Today, researchers apply effective methods to expand research and development of innovative molecules and optimized process conditions. This white paper discusses how scientists open new possibilities for control, optimization, and reporting of critical process conditions. Four case studies highlight how leading pharmaceutical companies impact synthesis lab performance:
- Identifying the ideal operating conditions for a successful triflation reaction
- Parameter control to avoid impurity formation during a guanidine reaction
- Central composite Design of Experiment (DoE) for guanidine reaction scale-up
- Inline reaction rate meter tracking a two-step lithium borohydride reduction