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A multistep continuous flow synthesis of cystic fibrosis medicine Ivacaftor

Abstract

Continuous flow ozonolysis method combined with multi-step flow sequence is developed for the synthesis of drug ivacaftor for the first time. Safe ozonolysis, continuous flow quadruple reaction to construct quinolone scaffold, inline extraction followed by continuous phase separation are the key features of present work. Feasibility of using a continuous mixed flow reactor commonly referred as CSTR (continuous stirred tank reactor) is also investigated for the relatively slow reaction segment. The current integrated multi-step flow synthesis can produce 7.2 g/day of the drug ivacaftor at laboratory scale, which is sufficient to treat 50 patient per day. The present route can also be used as a general route for the synthesis of other related drugs such as quinolone antibiotics.

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Publication details

The article was received on 19 Feb 2018, accepted on 15 May 2018 and first published on 16 May 2018


Article type: Paper
DOI: 10.1039/C8RE00025E
Citation: React. Chem. Eng., 2018, Accepted Manuscript
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    A multistep continuous flow synthesis of cystic fibrosis medicine Ivacaftor

    N. Vasudevan, M. K. Sharma, D. S. Reddy and A. Kulkarni, React. Chem. Eng., 2018, Accepted Manuscript , DOI: 10.1039/C8RE00025E

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