A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow. Issue 30 (20th June 2017)

• Record Type: Journal Article
• Authors: Lin, Hongkun; Dai, Chunhui; Jamison, Timothy F.; Jensen, Klavs F.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 30(2017)
• Page Start: 8870
• Page End: 8873
• Publication Date: 2017-06-20
• Subjects: aromatic substitution -- ciprofloxacin -- continuous flow -- multicomponent reactions -- multistep synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201703812
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Within a total residence time of 9 min, the sodium salt of ciprofloxacin was prepared from simple building blocks via a linear sequence of six chemical reactions in five flow reactors. Sequential offline acidifications and filtrations afforded ciprofloxacin and ciprofloxacin hydrochloride. The overall yield of the eight‐step sequence was 60 %. No separation of intermediates was required throughout the synthesis when a single acylation reaction was applied to remove the main byproduct, dimethylamine. Abstract : Rapid assembly of five building blocks to make the antibiotic ciprofloxacin was achieved in nine minutes in flow. A total of six reactions took place in five reactors to afford ciprofloxacin sodium salt. Simple offline pH adjustment, filtration and crystallization afforded ciprofloxacin hydrochloride crystal.