Preparation method of ciprofloxacin hydrochloride

Abstract

The invention discloses a preparation method of ciprofloxacin hydrochloride. The existing synthesis method generally uses isoamyl alcohol and the like as solvent, thus having the problems of strong smell, difficult biodegradation and higher environmental pollution. If the solvent such as the isoamyl alcohol and the like is used, more alkali insoluble substances and acidic insoluble substances are generated in recovery after the reaction, so that the insoluble substances are needed to be treated by purification through the steps such as alkali-dissolving heat-filtering call-back throw filter, acidic-dissolving heat-filtering call-back throw filter, salifying decoloration heat-filtering and the like, the process route is longer, and the product yield is lower. The preparation method of the ciprofloxacin hydrochloride selects the proper solvent as reaction medium, firstly leads cyclopropane carboxylic acid and piperazine to have piperazine reduction reaction and then leads the reaction product to be salified together with hydrochloric acid. In the reaction process, less alkali insoluble substances and acidic insoluble substances are generated in the reaction process, and the ciprofloxacin hydrochloride can be obtained by salifying decoloration heat-filtering, separation by crystallization, throw filter, rinsing and drying after being directly cooled and leached, so that the time for occupying equipment and the time of working procedures are shortened, and the production efficiency of a workshop is improved.

Description

technical field [0001] The invention relates to the field of medicines, in particular to a preparation method of ciprofloxacin hydrochloride. Background technique [0002] Fluoroquinolones have achieved great success in clinical anti-infective treatment due to their high-efficiency, broad-spectrum, and low-toxic antibacterial properties. Ciprofloxacin hydrochloride, developed by Bayer AG in 1981, is one of the excellent varieties. Ciprofloxacin Hydrochloride, English Name: Ciprofloxacin Hydrochloride, Molecular Formula: C 17 h 18 FN 3 o 3 ·HCl·H 2 O, molecular weight: 385.82, structural formula as follows: [0003] [0004] The method of effective medicinal component ciprofloxacin in the synthetic ciprofloxacin hydrochloride of raw material mainly contains with cyclopropanecarboxylic acid: [0005] 1) Direct substitution method: react piperazine with cyclopropanecarboxylic acid in a polar solvent (document: Ger Offen 1982, 3033157; CA 1982, 97: 55793u; Japanese Pate...

AI Technical Summary

Problems solved by technology

This preparation route has the following disadvantages: 1) the commonly used solvents are isoamyl alcohol, DMSO, DMF, etc. during the reduction of piperazine at present, which has a large odor, difficult biodegradation, and greater environmental pollution; 2) due to the higher boiling point of the solvent used, the The required temperature is mostly higher than 120°C, and the recovery time is long, and side reactions are prone to occur during the recovery process, which affects product quality and appearance; 3) If the above solvents are used, more alkali insoluble will be produced when the reaction is completed. Matters and acid-insoluble substances must be purified through steps such as alkali-soluble thermal filtration, callback rejection filtration, acid-soluble thermal filtration callback rejection filtration, and salt-forming decolorization thermal filtration. Not only the process route is long, but the product yield is low

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