CC BY 4.0 · Pharmaceutical Fronts 2020; 02(03): e128-e132
DOI: 10.1055/s-0040-1722215
Original Article

Continuous-Flow Processes for the Production of Floxacin Intermediates: Efficient C–C Bond Formation through a Rapid and Strong Activation of Carboxylic Acids

Shao-Zheng Guo
1   College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing 312000, People's Republic of China
Zhi-Qun Yu
2   Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
Wei-Ke Su
2   Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
› Author Affiliations
Funding We are grateful to the Public Projects of Zhejiang Province (Grant No. 2016C33071) and the National Natural Science Foundation of China (Grant No. 21676252 and 21406203) for financial support.


The development of highly efficient C–C bond formation methods for the synthesis of ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(dimethylamino)acrylate 1 in continuous flow processes has been described, which is based on the concept of rapid and efficient activation of carboxylic acid. 2,4-Dichloro-5-fluorobenzoic acid is rapidly converted into highly reactive 2,4-dichloro-5-fluorobenzoyl chloride by treating with inexpensive and less-toxic solid bis(trichloromethyl)carbonate. And then it rapidly reacts with ethyl 3-(dimethylamino)acrylate to afford the desired 1. This process can be performed under mild conditions. Compared with the traditional tank reactor process, less raw material consumption, higher product yield, less reaction time, higher operation safety ensured by more the environmentally friendly procedure, and process continuity are achieved in the continuous-flow system.

Publication History

Article published online:
31 December 2020

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