Preparation method of cefotiam hexetil hydrochloride

A technology for cefotiam hydrochloride and cefotiam hydrochloride, which is applied in the field of antibiotic preparation, can solve the problems of expensive raw materials, high isomer ratio, complicated purification means, etc., and achieves the advantages of simplifying the purification method and avoiding the use of chromatographic columns. Effect

Inactive Publication Date: 2012-04-25
HUNAN FANGSHENG PHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a preparation method of cefotiam pivoxil hydrochloride, to solve the technical problems of expensive raw materials, low yield, complicated purification means and high ratio of isomers

Method used

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  • Preparation method of cefotiam hexetil hydrochloride
  • Preparation method of cefotiam hexetil hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] 1) Add 120ml of N,N-dimethylformamide into a 250ml dry three-neck flask, cool down and stir. When the temperature of the solution in the bottle dropped to 0° C., 12 g (0.020 mol) of cefotiam hydrochloride was added and stirred to completely dissolve it.

[0059] 2) Lower the temperature. When the temperature of the solution in the bottle drops to -3°C, add 3.0 g (0.021 mol) of anhydrous potassium carbonate for the first time, and stir for 1 h. After 1 hour, the temperature was lowered. When the temperature in the bottle dropped to -5°C, 3.2 g (0.023 mol) of anhydrous potassium carbonate was added for the second time and stirred for 2 hours.

[0060] 3) Add 16.0 g (0.050 mol) of 1-iodoethylcyclohexyl carbonate, which has been cooled in an ice bath in advance, to the reaction solution. At this time, ensure that the temperature of the solution in the three-necked flask is -4 ° C ~ -6 ° C, and the reaction 8 minutes.

[0061] 4) after the reaction is finished, the reactio...

Embodiment 2

[0067] 1) Add 120ml of N,N-dimethylformamide into a 250ml dry three-neck flask, cool down and stir. When the temperature of the solution in the bottle dropped to 0° C., 12 g (0.020 mol) of cefotiam hydrochloride was added and stirred to completely dissolve it.

[0068] 2) Lower the temperature. When the temperature in the bottle drops to -5°C, add 6.2 g (0.044 mol) of anhydrous potassium carbonate at one time, and after stirring for 2.5 hours, add the 1-iodoethylcyclohexyl carbonate that has been cooled in a low-temperature bath to 16.5 g (0.055 mol) of the ester was added to the reaction solution, and at this time, the temperature of the solution in the three-neck flask was kept at -4°C-6°C, and the esterification reaction was carried out for 10 minutes.

[0069] 3) after the reaction finishes, the reaction solution is poured into the ice mixed solution of 300ml5% sodium chloride and 300ml ethyl acetate, the organic phase ethyl acetate solution is separated, the water phase i...

Embodiment 3

[0075] 1) Add 120ml of N,N-dimethylformamide into a 250ml dry three-neck flask, cool down and stir. When the temperature of the solution in the bottle dropped to 0° C., 12 g (0.020 mol) of cefotiam hydrochloride was added and stirred to completely dissolve it.

[0076] 2) Lower the temperature. When the temperature of the solution in the bottle drops to -3°C, add 3.5 g (0.025 mol) of anhydrous potassium carbonate for the first time, and stir for 1 h. After 1 hour, lower the temperature. When the temperature in the bottle drops to -5°C, add 3.2 g (0.023 mol) of anhydrous potassium carbonate for the second time. After stirring for 2 hours, add 1-iodoethylcyclohexylcarbonic 16.0 g (0.050 mol) of the ester was added to the reaction solution (the temperature of the solution in the three-neck flask was kept at -4°C-6°C), and the esterification reaction was carried out for 8 minutes.

[0077] 3) after the reaction is finished, the reaction solution is poured into the ice mixed solut...

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Abstract

The invention provides a preparation method of cefotiam hexetil hydrochloride. The method comprises: subjecting cefotiam hydrochloride and 1-iodoethyl cyclohexyl carbonate to an esterification reaction so as to obtain a cefotiam hexetil crude product, which is then purified into hydrochloride, thus obtaining cefotiam hexetil hydrochloride. In the esterification reaction, potassium carbonate is added, and cefotiam hydrochloride, potassium carbonate and 1-iodoethyl cyclohexyl carbonate are in a reaction mole ratio of 1:2.2-2.5:2.5-3. The method provided in the invention can reach a yield of 66% and make the isomer ratio less than 2%, or even to 1.3%. Employment of the preparation method in the invention can avoid usage of a chromatographic column and simplify the purification method, so that the method can be more suitable for industrial production needs.

Description

technical field [0001] The invention relates to the field of antibiotic preparation, in particular to a preparation method of cefotiam hydrochloride. Background technique [0002] Cefotiam hydrochloride structural formula: [0003] [0004] Cefotiam hydrochloride is a broad-spectrum antibacterial second-generation cephalosporin, which is highly stable to β-lactamase and can be used for the following infections caused by sensitive pathogenic bacteria Staphylococcus, pneumococcus, Haemophilus influenzae, etc. : Pharyngitis, acute bronchitis, chronic bronchitis, pneumonia, folliculitis, lymphatic arthritis, mastitis, otitis media, etc. [0005] When preparing cefotiam hydrochloride in the prior art, the potassium carbonate of cefotiam is mostly used as raw material to esterify with 1-iodoethyl cyclohexyl carbonate, and then the cefotiam hydrochloride obtained is salified with hydrochloric acid to obtain hydrochloric acid Cefotiam. However, cefotiam potassium carbonate is ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/04C07D501/12
Inventor 张庆华
Owner HUNAN FANGSHENG PHARMACEUTICAL CO LTD
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