101799-76-2Relevant articles and documents
A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow
Lin, Hongkun,Dai, Chunhui,Jamison, Timothy F.,Jensen, Klavs F.
, p. 8870 - 8873 (2017)
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.
A Consolidated and Continuous Synthesis of Ciprofloxacin from a Vinylogous Cyclopropyl Amide
Tosso, N. Perrer,Desai, Bimbisar K.,De Oliveira, Eliseu,Wen, Juekun,Tomlin, John,Gupton, B. Frank
, p. 3370 - 3376 (2019)
Ciprofloxacin is a broad-spectrum antibiotic that is recognized as one of the World Health Organization's Essential Medicines. It is particularly effective in the treatment of Gram-negative bacterial infections associated with urinary, respiratory, and gastrointestinal tract infections. A streamlined and high yielding continuous synthesis of ciprofloxacin has been developed, which employs a chemoselective C-acylation step that precludes the need for intermediate isolations, extractions, or purifications. The end-to-end process has a residence time of 4.7 min with a 15.8 g/h throughput at laboratory scale and an overall isolated yield of 83%.
On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
Armstrong, Cameron,Miyai, Yuma,Formosa, Anna,Thomas, Dale,Chen, Esther,Hart, Travis,Schultz, Victor,Desai, Bimbisar K.,Cai, Angela Y.,Almasy, Alexandra,Jensen, Klavs,Rogers, Luke,Roper, Tom
, p. 1524 - 1533 (2021/07/21)
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with necessary process changes identified and implemented before scaling for longer runs. These changes included implementing a continuous liquid-liquid extraction (CLLE) step and eliminating and replacing the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) initially used in the ring-closure step due to DBU plausibly forming a decomposition side product that negatively impacted the final product purity. Process conditions were scaled 1.5-2-fold in order to enable the ultimate project goal of producing enough crude ciprofloxacin within 24 h to manufacture 1000 250 mg tablets. Working toward this goal, several production-scale runs were carried out to assess the reproducibility and robustness of the finalized process conditions, with the first three steps being run continuously up to 22 h and the last two steps being run continuously up to 10 h. The end result is a process with a throughput of ～29 g/h (～700 g/24 h) with a crude product stream profile of 94 ± 2% and 34 ± 3 mg/mL after five chemical transformations across four reactors and one continuous CLLE unit operation with each intermediate step maintaining a purity >95% by HPLC.
