Examples of continuous flow reactions in the laboratory setting are becoming commonplace in pharmaceutical drug substance research. Developing these processes for robust commercialization and identifying the scale-up parameters remains a challenge. An aldol reaction in the formation of an active pharmaceutical ingredient intermediate was developed in flow at the milliliter scale. Research focused on identifying conditions that led to robust and stable operating conditions. Desired reaction performance was achieved in various mixers across reactor scales by identifying conditions that led to similar flow regimes. Conditions from the lab were transferred to the pilot plant to successfully process ∼200 kg of the starting material.

• Merck & Co., Inc.

• Intermediate
• API

1. Aldol reactions
2. API
3. continuous flow reaction
4. Intermediate
5. mixing sensitive reaction
6. Research Article
7. Scale-up