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Method for preparing high-quality levofloxacin hydrochloride

A high-quality technology of levofloxacin hydrochloride, applied in organic chemistry and other directions, can solve the problems of increased post-processing workload and three wastes, poor environmental protection and economy, no specific introduction, etc., to reduce environmental pollution, industrial raw material consumption, and low production costs. , the effect of simplifying the process

Inactive Publication Date: 2017-09-15
TAICANG HONGSHAN ENVIRONMENTAL PROTECTION TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the synthesis process reported in the literature also has many defects, which are as follows: (1) the first step does not separate triethylamine hydrochloride, and directly enters the second step, and the waste water produced will contain triethylamine hydrochloride and diethylamine hydrochloride at the same time. Methylamine acetate; (2) In the second step, toluene is dried with a desiccant, which will produce solid waste; (3) In the third step, potassium carbonate and toluene system are used. Because the solubility of potassium carbonate inorganic salts in toluene is too poor, the reaction It is not ideal, the yield is unstable, and the salt and the product are precipitated at the same time after the reaction, which increases the post-processing workload and the three wastes; (4) The fourth step is not specifically introduced
The fifth step is the reaction of levofloxacin and N-methylpiperazine in DMSO. DMSO is used as a solvent, and the boiling point is too high, which increases the energy consumption of recovery; (5) Finally, the crude product of levofloxacin is refined with 95% ethanol, and the overall process will produce A large amount of industrial wastewater used for washing and unrecyclable salts are poor in environmental protection and economy

Method used

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  • Method for preparing high-quality levofloxacin hydrochloride

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Such as figure 1 The synthetic method of shown levofloxacin hydrochloride comprises the following steps:

[0045] (1) Preparation of 3-(2-hydroxy-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate

[0046] Add 29.2g of N,N ethyl dimethylaminoacrylate, 22.7g of triethylamine and 340ml of toluene into a three-necked flask, heat to 50°C under stirring, slowly add a solution of 42.5g of tetrafluorobenzoyl chloride / toluene, dropwise Add for 1.5 hours, keep warm for 3 hours after dropping, convert 97%, cool, filter about 24.2g of triethylamine hydrochloride, wash the filter cake of triethylamine hydrochloride with a small amount of toluene, heat the filtrate to 50°C, add 15g of triethylamine hydrochloride dropwise L-2-Aminopropanol, dripped in half an hour, raised the temperature to 90°C, kept it warm for 1 hour, the conversion was 98%, cooled, washed twice with water, the toluene phase was separated, spin-dried and dehydrated, diluted with DMF to 250ml, liquid...

Embodiment 2

[0053] Such as figure 1 The synthetic method of shown levofloxacin hydrochloride comprises the following steps:

[0054] (1) Preparation of 3-(2-hydroxy-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate

[0055] Add 29.2g of N,N ethyl dimethylaminoacrylate, 20.2g of triethylamine and 340ml of toluene into a three-necked flask, heat it to 40°C under stirring, slowly add a solution of 46.8g of tetrafluorobenzoyl chloride / toluene dropwise, drop Add for 1 hour, keep warm for 2 hours after dropping, convert 96%, cool, filter about 24.8g of triethylamine hydrochloride, wash the filter cake of triethylamine hydrochloride with a small amount of toluene, heat the filtrate to 40°C, add 18.4g dropwise The L-2-aminopropanol was dropped in half an hour, heated to 90°C, kept warm for 0.5 hours, converted 98%, cooled, washed three times with water, separated into toluene phases, spin-dried and dehydrated, diluted with DMF to 250ml, liquid The phase purity is 99.22%.

[00...

Embodiment 3

[0062] Such as figure 1 The synthetic method of shown levofloxacin hydrochloride comprises the following steps:

[0063] (1) Preparation of 3-(2-hydroxy-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate

[0064] Add 29.2g of N,N ethyl dimethylaminoacrylate, 24.3g of triethylamine and 340ml of toluene into a three-necked flask, heat to 60°C under stirring, slowly add 45g of tetrafluorobenzoyl chloride / toluene solution dropwise, dropwise After 2 hours, keep warm for 4 hours after dripping, convert 97%, cool, filter about 25.2g of triethylamine hydrochloride, wash the filter cake of triethylamine hydrochloride with a small amount of toluene, heat up the filtrate to 60°C, add dropwise 17g of L -2-Aminopropanol, drop it in half an hour, raise the temperature to 90°C, keep it warm for 1.5 hours, the conversion is 98%, cool, wash twice with water, separate the toluene phase, spin dry and dehydrate, add DMF to dilute to 250ml, liquid phase The purity is 99.41%.

[...

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Abstract

The invention provides a method for preparing high-quality levofloxacin hydrochloride, comprising 3-(2-hydroxyl-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)- Preparation of ethyl acrylate, preparation of levocyclamic acid and preparation of levofloxacin hydrochloride, the method is simple, the production cost is low, the product yield is high, the quality is good, the green economy is environmentally friendly, the discharge of three wastes is small, and most of the by-products are effectively separated and recovered at the same time Utilization is convenient for industrialized production and has great popularization significance.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a method for preparing high-quality levofloxacin hydrochloride. Background technique [0002] Fluoroquinolones have achieved great success in clinical anti-infective treatment due to their high efficiency, broad antibacterial spectrum and low toxicity. The chemical name of levofloxacin hydrochloride is (s)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-[4-methyl-1-piperazinyl]-7-oxo- 7-hydropyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate hydrochloride. [0003] At present, the domestic industrialized production of levofloxacin is mainly based on (2,3,4,5)-tetrafluorobenzoic acid as raw material, after acid chlorination, coupling with N,N-dimethylaminoethyl acrylate, and replacement with L-aminopropanol. , Cyclization, hydrolysis and condensation with N-methylpiperazine refined. In 2005, "Journal of Chemical Engineering of Universities" No. 5, Volume 19, dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/06
CPCC07D498/06
Inventor 刘露
Owner TAICANG HONGSHAN ENVIRONMENTAL PROTECTION TECH CO LTD
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