Continuous flow synthesis of a pharmaceutical intermediate: a computational fluid dynamics approach

Area of Science:

• Chemical Engineering
• Process Chemistry
• Computational Science

Background:

• Continuous flow chemistry offers enhanced efficiency for active pharmaceutical ingredient (API) synthesis.
• Process optimization is challenging due to numerous variables influencing reaction outcomes.

Purpose of the Study:

• To compare computational fluid dynamics (CFD) simulations with experimental results for continuous flow reactor optimization.
• To validate CFD as a tool for identifying key reaction parameters and predicting product yield.

Main Methods:

• Utilized a screening design of experiments to compare CFD simulations and experimental data.
• Analyzed reactor residence time and temperature as critical factors affecting product yield.

Main Results:

• Both CFD and experiments identified residence time and temperature as the most significant factors for product yield.
• A strong correlation was observed between predicted and experimental percent yields, with absolute differences as low as 2.4% and up to 19.1%.
• CFD showed a tendency to underestimate yields at low residence times and overestimate at higher residence times.

Conclusions:

• CFD simulations are a valuable tool for designing continuous flow tube reactors.
• CFD significantly reduces the need for extensive experimentation in API synthesis.
• CFD aids in identifying critical process parameters and predicting reaction performance.