(758a) Development and Implementation of a Process to Control Off-Gassing | AIChE

(758a) Development and Implementation of a Process to Control Off-Gassing


Lee, A. G. - Presenter, Bristol-Myers Squibb Company
Lo, E. T., Bristol-Myers Squibb Company
Natalie, K., Bristol-Myers Squibb Co,
Vu, T., Bristol-Myers Squibb Company
Rossano, L., Bristol-Myers Squibb Company

The use of the tert-butyloxycarbonyl (BOC) moiety is a highly effective protection strategy for amines in the synthesis of small molecule active pharmaceutical ingredients. While evaluating these chemistries, the evolution rate of carbon dioxide and other volatile byproducts from these reactions is a major consideration for scale up. In our development of a BOC protection reaction to produce a pharmaceutical intermediate, the physical property of a solid intermediate severely hindered mixing in the vessel. As the reaction progressed, changes to the solid’s physical property resulted in rapid uncontrolled off-gassing. We discuss the development of a process using acid and base charge equivalents, charge rate and pH to address the solid intermediate formation and gas evolution. We scaled up the process in the kilo plant to demonstrate a range of process parameters which yielded good control over gas evolution while maintaining acceptable quality and yield.