Abstract
In pharmaceutical industry, cryogenic reaction is frequently used for the organometallic reaction or stereoselective synthesis of active pharmaceutical ingredient and its intermediate. Cryogenic condition is required for above reactions because of thermal instability of organometallic compound or improvement of the selectivity. This paper focuses on continuous cryogenic organic reactions using mini size multi-stage reactors (their volume range is from 10-6 to 10-3m3). Mini size reactor has many advantages such as high heat exchange efficient and fast mixing etc. similarly to micro reactor. In addition, mini size reactor has an advantage of operability over micro-scale reactor. Reactions of this study are two successive cryogenic reactions, which are highly exothermic, therefore a large amount of heat removal is required. Currently, the production scale reaction is carried out by batch method, and the temperature control is performed by slow charging of reagents and slow addition of reactant, which causes the yield loss especially in the 2nd reaction. Herein, the reactions have been demonstrated by using mini size multi-stage reactor and compared the results for the product yield, by- products and stereoselectivity of product with a production scale batch reaction. The results and issues are discussed in this study.
