Process for crystallizing moxifloxacin hydrochloride

A technology of moxifloxacin hydrochloride and moxifloxacin, which is applied in the crystallization process field of moxifloxacin hydrochloride, can solve the problem of unfavorable quality stability of moxifloxacin hydrochloride, poor crystal form and quality of moxifloxacin hydrochloride, and affect the normal operation of wastewater treatment stations function and other issues, to achieve the effect of high product yield, good volatility, and reduced water content

Active Publication Date: 2011-04-27
SHANGYU JINGXIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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

Method used

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  • Process for crystallizing moxifloxacin hydrochloride
  • Process for crystallizing moxifloxacin hydrochloride
  • Process for crystallizing moxifloxacin hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032]Put 30 grams of moxifloxacin malate (0.0560 mol), 25 grams of water and 30 grams of ethylene glycol mono-n-propyl ether into a 500 ml three-necked reaction flask in sequence, stir, heat to 75-80 °C, dissolve and add 0.2 gram of activated carbon, decolorize at 75-80°C for 30 minutes, filter while hot, and collect the filtrate. Heat the filtrate to 75-80°C, add 9 ml of concentrated hydrochloric acid dropwise to the filtrate until the system pH=1.5-2.5, keep stirring for 0.5 hours, fully analyze the crystallization at 75-80°C, and then start to drop 180 g of ethylene glycol mono For n-propyl ether, drop it within 1 hour, then start to lower the temperature, and keep warm and crystallize for 1.5 hours at 0~-2°C. Finished, suction filtered, rinsed the product with 35 grams of 90% ethanol, sucked dry, and vacuum-dried for 6 to 7 hours at 60 to 65° C. to obtain 22.7 grams of moxifloxacin hydrochloride (I), with a molar yield of 92.6%.

Embodiment 2

[0034] Put 30 grams of moxifloxacin tartrate (0.0544 moles), 30 grams of water and 25 grams of ethylene glycol dimonoether into a 500 ml three-necked reaction flask in sequence, stir, heat to 75-80 ° C, add 0.2 grams of activated carbon after dissolving , decolorized at 75-80°C for 30 minutes, filtered while hot, and collected the filtrate. Heat the filtrate to 75-80°C, add 9 ml of concentrated hydrochloric acid dropwise to the filtrate until the pH of the system is 1.5-2.5, keep stirring for 0.5 hours, fully analyze the crystallization at 75-80°C, and then start to add 190 g of ethylene glycol di Monoether, drop it within 1 hour, then start to lower the temperature, and keep warm and crystallize for 1.5 hours at 0~-2°C. Finish, suction filtration, be 10% ethylene glycol dimethyl ether solution rinsing product with 35 grams of water content, suck dry, vacuum-dry 5~6 hours at 50~55 ℃, obtain 22.9 grams of moxifloxacin hydrochloride (I ), the molar yield is 96.1%.

Embodiment 3

[0036] Put 30 grams of moxifloxacin mandelate (0.0542 mol), 25 grams of water and 27 grams of ethylene glycol mono-n-propyl ether into a 500 ml three-necked reaction flask in turn, stir, heat to 75-80 °C, dissolve and add 0.2 gram of activated carbon, decolorize at 75-80°C for 30 minutes, filter while hot, and collect the filtrate. Heat the filtrate to 75-80°C, add 9 ml of concentrated hydrochloric acid dropwise to the filtrate until the system pH=1.5-2.5, keep stirring for 0.5 hours, fully analyze the crystallization at 75-80°C, and then start to drop 190 g of ethylene glycol mono For n-propyl ether, drop it within 1 hour, then start to lower the temperature, and keep warm and crystallize for 1.5 hours at 0~-2°C. Finished, suction filtered, rinsed the product with 35 grams of 90% alcohol, drained, and dried in vacuum at 60 to 65° C. for 6 to 7 hours to obtain 22.1 grams of moxifloxacin hydrochloride (I), with a molar yield of 93.1%.

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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...

Claims

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Application Information

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IPC IPC(8): C07D471/04
Inventor 张永塘李先何梁水东
Owner SHANGYU JINGXIN PHARMA
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