Synthesis of treprostinil: key Claisen rearrangement and catalytic Pauson-Khand reactions in continuous flow
| Autor: | Gema Domínguez, Javier Pérez-Castells, Jaime Blanco-Urgoiti, Jorge García-Lacuna |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Continuous flow Organic Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry 0104 chemical sciences Catalysis Claisen rearrangement chemistry.chemical_compound chemistry Yield (chemistry) medicine Phenol Physical and Theoretical Chemistry Selectivity Plug flow reactor model Treprostinil medicine.drug |
| Zdroj: | Organicbiomolecular chemistry. 17(43) |
| ISSN: | 1477-0539 |
| Popis: | A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson–Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection–deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|