(121d) Development of Continuous Homogeneous Hydrogenation Process for Pharmaceuticals Using a Flow Reactor | AIChE

(121d) Development of Continuous Homogeneous Hydrogenation Process for Pharmaceuticals Using a Flow Reactor

Authors 

Gerceker, D., Abbvie
Storer, G., AbbVie
Kotecki, B., AbbVie
Harper, K., AbbVie
Chaaya, E., AbbVie
Shekhar, S., AbbVie
Diwan, M., Abbvie Inc.
In past decade there has been significant interest in the development of continuous processes in the pharmaceutical industry. Key drivers for continuous processing are product quality improvement, yield and process robustness, footprint reduction of processing area and increased process safety. Hydrogenations are commonly used in synthesis of pharmaceutical intermediates and active pharmaceutical ingredients. Types of hydrogenations include removal of protecting groups such as benzyl groups, reduction of nitro compounds and asymmetric hydrogenations. In this work we have demonstrated:

  • Application of a laboratory scale tubular reactor for development and scale-up of a continuous asymmetric hydrogenations process.
  • The effect of operating parameters such as pressure, gas to liquid ratio, temperature, catalyst loading and residence time of the substrate on enantioselectivity and product quality, are studied to develop a scalable and robust process.

A ‘Fit for purpose’ model was developed and found to be very effective in efficiently identifying the optimal reaction conditions, assessing risk to product CQAs, and increasing overall robustness.

Disclosures:

All authors are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.