Phase Separation Macrocyclization in a Complex Pharmaceutical Setting: Application toward the Synthesis of Vaniprevir.
| Autor: | Godin É; Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal , CP 6128 Station Downtown, Montréal, Québec, H3C 3J7 Canada., Bédard AC; Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal , CP 6128 Station Downtown, Montréal, Québec, H3C 3J7 Canada., Raymond M; Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal , CP 6128 Station Downtown, Montréal, Québec, H3C 3J7 Canada., Collins SK; Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal , CP 6128 Station Downtown, Montréal, Québec, H3C 3J7 Canada. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of organic chemistry [J Org Chem] 2017 Jul 21; Vol. 82 (14), pp. 7576-7582. Date of Electronic Publication: 2017 Jul 05. |
| DOI: | 10.1021/acs.joc.7b01308 |
| Abstrakt: | A phase separation/continuous flow strategy employing an oxidative Glaser-Hay coupling of alkynes has been applied toward the synthesis of the macrocyclic core of complex pharmaceutical vaniprevir. The phase separation/continuous flow strategy afforded similar yields at 100-500 times the concentration and at shorter reaction times than common slow addition/high dilution techniques. In addition, dendritic PEG cosolvents were employed in the phase separation strategy for the first time and shown to allow productive macrocyclization at concentrations up to 200 mM. |
| Databáze: | MEDLINE |
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