Green Solvents for Eco-Friendly Synthesis of Dimethindene: A Forward-Looking Approach

被引：4

作者：

Quivelli, Andrea Francesca ^{[1
]}

Rossi, Federico Vittorio ^{[2
]}

Alario, Chiara ^{[2
]}

Sannicolo, Francesco ^{[2
]}

Vitale, Paola ^{[1
]}

Garcia-Alvarez, Joaquin ^{[3
]}

Perna, Filippo Maria ^{[1
]}

Capriati, Vito ^{[1
]}

机构：

[1] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Consorzio CINMPIS, Via E Orabona 4, I-70125 Bari, Italy

[2] Lab Alchemia Srl, Via San Faustino 68, I-20134 Milan, Italy

[3] Ctr Innovac Quim Avanzada ORFEO CINQA, Fac Quim, Lab Quim Sintet Sostenible QuimSisSos, Dept Quim Organ & Inorgan,IUQOEM, Julian Claveria 8, Oviedo 33006, Spain

来源：

MOLECULES | 2022年 / 27卷 / 21期

关键词：

dimethindene; deep eutectic solvents; API synthesis; synthetic methodologies; green chemistry; cyclopentyl methyl ether; 2-Methyltetrahydrofuran; CHEMISTRY; H-1-ANTIHISTAMINES;

D O I：

10.3390/molecules27217594

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：11

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