Integrating continuous flow reaction and work-up: chiral amine resolution, separation and purification using a novel...

Area of Science:

• Chemical Engineering
• Organic Chemistry
• Process Chemistry

Background:

• Continuous flow reactions offer advantages over batch processes.
• Integrating reaction and work-up steps is crucial for maximizing efficiency.
• Amine resolution is a key step in synthesizing chiral compounds.

Purpose of the Study:

• To design and demonstrate a continuous process for amine resolution.
• To integrate liquid-liquid extraction, back-extraction, and crystallization into a continuous flow system.
• To achieve high yield and enantiomeric purity of chiral amines.

Main Methods:

• Enzymatic resolution of (rac)-1-phenylethylamine using immobilized lipase in a fixed-bed reactor.
• Continuous liquid-liquid extraction and back-extraction using novel separators.
• Crystallization purification of the desired amine enantiomer.

Main Results:

• The continuous process achieved 50% conversion and 96% enantiomeric excess (ee) for the (R)-amide.
• The (S)-amine was isolated with 43% yield and >99% ee.
• The integrated system utilized mild conditions and green solvents, minimizing waste.

Conclusions:

• A fully continuous process for amine resolution and purification was successfully developed.
• The integration of multiple separation techniques in flow enhances efficiency and product purity.
• This approach offers a sustainable and scalable method for chiral amine production.