A multi-step continuous flow synthesis of the cystic fibrosis medicine ivacaftor
| Autor: | Mrityunjay K. Sharma, Amol A. Kulkarni, D. Srinivasa Reddy, N. Vasudevan |
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| Rok vydání: | 2018 |
| Předmět: |
Fluid Flow and Transfer Processes
Chromatography Continuous phase modulation 010405 organic chemistry Chemistry Reaction step Continuous flow Process Chemistry and Technology Continuous stirred-tank reactor Laboratory scale 010402 general chemistry 01 natural sciences Catalysis 0104 chemical sciences Ivacaftor Mixed flow Flow (mathematics) Chemistry (miscellaneous) medicine Chemical Engineering (miscellaneous) medicine.drug |
| Zdroj: | Reaction Chemistry & Engineering. 3:520-526 |
| ISSN: | 2058-9883 |
| DOI: | 10.1039/c8re00025e |
| Popis: | A continuous flow ozonolysis method combined with a multi-step flow sequence is developed for the synthesis of the drug ivacaftor for the first time. Safe ozonolysis, a continuous flow quadruple reaction to construct a quinolone scaffold, and inline extraction followed by continuous phase separation are the key features of the present work. The feasibility of using a continuous mixed flow reactor, commonly referred to as a continuous stirred tank reactor (CSTR), is also investigated for the relatively slow reaction step. The current integrated multi-step flow synthesis can produce 7.2 g of the drug ivacaftor per day on a laboratory scale, which is sufficient to treat 50 patients per day. The present route can also be used as a general route for the synthesis of other related drugs such as quinolone antibiotics. |
| Databáze: | OpenAIRE |
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