title: Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D-Printed Mesoreactors.
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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Porta
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Brenna
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Puglisi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.
authors.forename: Maurizio
authors.identifier: 0000-0002-9568-9642
authors.initials: M
authors.lastname: Benaglia
mesh_terms: D002384:Catalysis; D004867:Equipment Design; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry; D006865:Hydrogenation; D008680:Metaraminol / Q000138:chemical synthesis* / Q000737:chemistry; D008729:Methoxamine / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry; D010665:Phenylpropanolamine / Q000138:chemical synthesis* / Q000737:chemistry; D066330:Printing, Three-Dimensional; D013237:Stereoisomerism
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D009574:Nitro Compounds; C560828:nitroaldol; D010665:Phenylpropanolamine; D008680:Metaraminol; D008729:Methoxamine
keywords: 3D printing; amino alcohols; flow reactors; nitroaldol reactions; stereoselective catalysis