| Title: | Green Solvents for Eco-Friendly Synthesis of Dimethindene: A Forward-Looking Approach |
| Author(s): | Quivelli AF; Rossi FV; Alario C; Sannicolo F; Vitale P; Garcia-Alvarez J; Perna FM; Capriati V; |
| Address: | "Dipartimento di Farmacia-Scienze del Farmaco, Universita degli Studi di Bari 'Aldo Moro', Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, I-70125 Bari, Italy. Laboratori Alchemia S.r.l., Via San Faustino 68, I-20134 Milan, Italy. Laboratorio de Quimica Sintetica Sostenible (QuimSisSos), Departamento de Quimica Organica e Inorganica, (IUQOEM), Centro de Innovacion en Quimica Avanzada (ORFEO-CINQA), Facultad de Quimica, Julian Claveria, 8, 33006 Oviedo, Spain" |
| DOI: | 10.3390/molecules27217594 |
| ISSN/ISBN: | 1420-3049 (Electronic) 1420-3049 (Linking) |
| Abstract: | "Dimethindene is a selective histamine H(1) antagonist and is commercially available as a racemate. Upon analyzing the synthetic pathways currently available for the industrial preparation of dimethindene, we set up a sustainable approach for the synthesis of this drug, switching from petroleum-based volatile organic compounds (VOCs) to eco-friendly solvents, such as 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) belonging to classes 3 and 2, respectively. Beyond decreasing the environmental impact of the synthesis (E-factor: 24.1-54.9 with VOCs; 12.2-22.1 with 2-MeTHF or CPME), this switch also improved the overall yield of the process (from 10% with VOCs to 21-22% with 2-MeTHF or CPME) and remarkably simplified the manual operations, working under milder conditions. Typical metrics applied at the first and second pass, according to the CHEM21 metrics toolkit, were also calculated for the whole synthetic procedure of dimethindene, and the results were compared with those of the classical procedure" |
| Keywords: | *Dimethindene Solvents *Methyl Ethers Histamine 2-Methyltetrahydrofuran API synthesis cyclopentyl methyl ether deep eutectic solvents dimethindene green chemistry synthetic methodologies; |
| Notes: | "MedlineQuivelli, Andrea Francesca Rossi, Federico Vittorio Alario, Chiara Sannicolo, Francesco Vitale, Paola Garcia-Alvarez, Joaquin Perna, Filippo Maria Capriati, Vito eng 2017A5HXFC_002/Ministero dell'Universita e della Ricerca/ CTQ2016-75986-P/MCIN/AEI/10.13039/501100011033/ RED2018-102387-T/MCIN/AEI/10.13039/501100011033/ PID2020-113473GB-I00/MCIN/AEI/10.13039/501100011033/ Switzerland 2022/11/12 Molecules. 2022 Nov 5; 27(21):7594. doi: 10.3390/molecules27217594" |
