Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D‐Printed Mesoreactors

Abstract

Abstract 3D‐printed flow reactors were designed, fabricated from different materials (PLA, HIPS, nylon), and used for a catalytic stereoselective Henry reaction. The use of readily prepared and tunable 3D‐printed reactors enabled the rapid screening of devices with different sizes, shapes, and channel dimensions, aimed at the identification of the best‐performing reactor setup. The optimized process afforded the products in high yields, moderate diastereoselectivity, and up to 90 % ee . The method was applied to the continuous‐flow synthesis of biologically active chiral 1,2‐amino alcohols (norephedrine, metaraminol, and methoxamine) through a two‐step sequence combining the nitroaldol reaction with a hydrogenation. To highlight potential industrial applications of this method, a multistep continuous synthesis of norephedrine has been realized. The product was isolated without any intermediate purifications or solvent switches.