Process for crystallizing moxifloxacin hydrochloride

Abstract

The invention discloses a process for crystallizing moxifloxacin hydrochloride. In the conventional crystallization methods, the yield of the moxifloxacin hydrochloride is lower, the amount of organic solvents residual in the moxifloxacin hydrochloride is larger, a crystallization solvent plays a role in inhibiting the growth of microbes and even poisoning the microbes, and normal function of a wastewater treatment station is influenced. The technical scheme comprises the following steps of: adding water and glycol alkyl ether successively into moxifloxacin, organic acid salt of the moxifloxacin or inorganic weak-acid salt of the moxifloxacin, stirring for dissolving at the temperature of between 40 and 100 DEG C, decoloring, filtering and collecting filtrate; heating the filtrate to the temperature of between 40 and 100 DEG C, dripping concentrated hydrochloric acid, and stirring to separate out a crystal; and dripping the glycol alkyl ether, stirring, cooling, keeping the temperature, crystallizing, performing suction filtration, rinsing, and drying to prepare the moxifloxacin hydrochloride crystal. Due to the crystallization solvent, the moxifloxacin hydrochloride is more completely separated out in a crystallization system, and the product yield is higher.

Description

technical field [0001] The invention relates to the preparation of antibacterial drugs, in particular to a crystallization process of moxifloxacin hydrochloride. Background technique [0002] Moxifloxacin [Moxifloxacin, 1-cyclopropyl-7-(S,S-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-8-methoxy-4 -Oxo-1,4-dihydro-3-quinoline carboxylic acid] is the fourth generation fluoroquinolone antibacterial drug, it was developed by Bayer AG of Germany, it was listed in Germany for the first time in September 1999, and it was listed in the United States in December of the same year . Its chemical structure is obviously different from other fluoroquinolones, and a methoxy group is introduced into the 8-position carbon atom of its molecular structure. This structural feature not only has the antibacterial activity of other quinolones against Gram-negative bacteria, but also enhances the antibacterial effect against Gram-positive bacteria and atypical pathogenic bacteria, and has almost n...

AI Technical Summary

Problems solved by technology

[0015] First, the Chinese patent CN1279683 applied by Bayer, the first research unit, used the water-C1~C2 alkanol mixture to recrystallize to prepare moxifloxacin hydrochloride, especially the water-ethanol mixture as the recrystallization solvent , so that the process has obvious advantages in environmental protection in the process of industrial application, and the treatment of the recrystallization mother liquor is simple, but due to the high polarity of the lower monohydric alcohols, the solubility of moxifloxacin hydrochloride is strong, so that the yield of moxifloxacin hydrochloride in the preparation process low

[0016] Second, as represented by the world patent WO2006134491 and the US patent US2005272768, organic solvents with higher boiling points such as C3-C4 alcohols, C3-C7 ketones and C3-C7 esters are used as crystallization solvents for the preparation of moxifloxacin hydrochloride. The environment-friendly smell is heavy during the chemicalization process; not only the temperature is too high during the vacuum drying process of moxifloxacin hydrochloride, which is not conducive to the stability of the quality of moxifloxacin hydrochloride before and after drying, but also the amount of organic solvent remaining in moxifloxacin hydrochloride is relatively high, which is difficult to meet Requirements of ICH and other regulations

[0017] The 3rd, take the U.S. Patent US2006252789 and the world patent WO2008059521 as representative to adopt dichloromethane, trichloromethane, dichloroethane etc. as the crystallization solvent of preparing moxifloxacin hydrochloride, the obtained moxifloxacin hydrochloride crystal form and quality are relatively high Poor, once the halogenated alkanes used are discharged into the wastewater, not only the microorganisms are difficult to degrade, but also the growth of microorganisms will be inhibited or even poisoned, affecting the normal function of the wastewater treatment station

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