Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine
| Autor: | Anne-Catherine Bédard, Ashley R. Longstreet, Joshua Britton, Robert W. Hicklin, Hideki Moriguchi, William H. Green, Yuran Wang, Timothy F. Jamison |
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| Rok vydání: | 2017 |
| Předmět: |
Atropine
Green chemistry Commodity chemicals Clinical Biochemistry Pharmaceutical Science E factor Pharmacology 010402 general chemistry 01 natural sciences Biochemistry World health Drug Discovery medicine Molecular Biology Active ingredient Diazepam 010405 organic chemistry Continuous flow Chemistry Organic Chemistry Green Chemistry Technology Hydrogen-Ion Concentration 0104 chemical sciences Solvents Molecular Medicine Biochemical engineering medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 25:6233-6241 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2017.02.002 |
| Popis: | Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9. |
| Databáze: | OpenAIRE |
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