A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow

Hongkun Lin; Chunhui Dai; Timothy F Jamison; Klavs F Jensen

doi:10.1002/anie.201703812

A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow

Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8870-8873. doi: 10.1002/anie.201703812. Epub 2017 Jun 20.

Authors

Hongkun Lin¹, Chunhui Dai², Timothy F Jamison², Klavs F Jensen¹

Affiliations

¹ Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
² Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.

PMID: 28561939
DOI: 10.1002/anie.201703812

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.

Keywords: aromatic substitution; ciprofloxacin; continuous flow; multicomponent reactions; multistep synthesis.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acylation
Chemistry Techniques, Synthetic / methods*
Ciprofloxacin / chemical synthesis*
Ciprofloxacin / chemistry
Molecular Structure
Time Factors

Substances

Ciprofloxacin