Abstract

Microfluidic Approaches for Scale-up Chemical Production via Numbering-up & Ultrafast Chemistry

Dong-Pyo Kim, Yonsan Chaired Professor, Center for Intelligent Microprocess of Pharmaceutical Synthesis, POSTECH

Continuous-flow technology is emerging for efficient, sustainable and safe synthesis of drug and the precursors. In here, scale-up chemical production are efficiently demonstrated by adopting both approaches of numbering-up microreactors and ultrafast chemical synthesis at high flow rates. Firstly, various numbering-up microreactor systems were designed and manufactured with stainless steel metal or polymer films. The compact and robust reactors demonstrated scale-up production of several drug compounds via azide-alkyne reaction, fast synthesis of organophosphates. Moreover, photocatalysis in a multi-capillary assembly system, 3D printed reactors were used to improve the synthetic productivity. Alternatively, ultrafast synthetic approaches were performed by taming the lithiated flash chemistry in unique microreactors at high flow rates, which envisions facile scale-up production of drugs. Unique design of a chip microreactor enabled submillisecond mixing time even at low temperatures, which was used for outpacing rapid intramolecular rearrangements such as anionic Fries rearrangement to attain high chemoselectivity. And 3D-printed stainless steel microreactor with circular shape of cross-sectional fluidic channel enhanced the intramolecular control for higher yield of the un-rearranged product. Further, a 16 stacked reactor system of circular channel structure with superior mixing efficiency was alternatively devised to synthesize commercial Letrozole drug by newly developed 3 steps route, including ~10 milliseconds of flash chemistry.