Preparation method for cefotiam hydrochloride

A technology of cefotiam hydrochloride and hydrochloric acid, applied in a new preparation field, can solve problems such as unfavorable production, research and utilization, complicated reaction process, poor reaction degree, etc., achieve less residual impurities, high content, and reduce environmental protection pressure Effect

Inactive Publication Date: 2018-11-02
SHANGHAI NEW ASIA PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The above-mentioned reaction process is complicated, requires multiple purification treatments, and its reaction degree is poor, the yield is low, and the color grade of the obtained product is relatively high, and the impurities are relatively high, which is not conducive to subsequent production, research and utilization.

Method used

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  • Preparation method for cefotiam hydrochloride
  • Preparation method for cefotiam hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0035] Example 1-1, Preparation of aminothiazole acetyl chloride hydrochloride (ATC.HCL).

[0036] Add 120 ml of acetonitrile to the reactor to control the temperature below 10 degrees, and add DMF. 50 g of phosphorus oxychloride was added dropwise, and 60 g of aminothiazole acetic acid hydrochloride was added after dropping, and the reaction was timed for 10-20 hr, then the temperature was lowered, and 120 ml of acetonitrile was added. Crystal growth 1.0-2.0hr. Centrifuged aminothiazole acetyl chloride hydrochloride (ATC.HCL), high pressure liquid phase purity 98%

Embodiment 1-2

[0038] Add 100 ml of acetonitrile to the reactor to control the temperature below 10 degrees, and add DMF. Add 60 g of thionyl chloride dropwise, and add 60 g of aminothiazole acetic acid hydrochloride after dropping, time the reaction for 4-6 hours, then lower the temperature, and add 100 ml of acetonitrile. Crystal growth 1.0-2.0hr. Centrifuged aminothiazole acetyl chloride hydrochloride (ATC.HCL), high pressure liquid phase purity 97.5%

Embodiment 2

[0040] At room temperature, 100 ml of dimethyl carbonate, 40 g of 7-aminocephalosporanic acid, and 15 g of MTZ were added. Add 15g of boron trifluoride-dimethyl carbonate complex and 5g of methanesulfonic acid at the same temperature, control the temperature at 35-40°C and time the reaction for 1-2.0hr, then cool down to below 20°C and add 320ml of pure water for hydrolysis, then add 300ml Carbon tetrachloride was extracted for 10 minutes, and the layers were separated. Then add activated carbon to decolorize for 20min and filter. Control the temperature of the filtrate below 5°C, add triethylamine dropwise to adjust the pH to 7.0-8.0, then add ATC.HCL (Example 1-1), and react at a time below 5°C for 1-2.0 hours. After the reaction is complete, add Add 60ml of concentrated hydrochloric acid, then add activated carbon for decolorization for 20min, filter, add 1400-1500ml of acetone dropwise to the filtrate, add seed crystals to grow the crystal, after the crystallization is co...

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Abstract

The invention provides a preparation method for cefotiam hydrochloride. The preparation method is characterized by comprising the following steps; adopting boron trifluoride complex to catalyze condensation reaction of 7-aminocephalosporanic acid and 1-(2-dimethyl aminoethyl)-1H-5-tetrazole-thione in case of taking dimethyl carbonate as a solvent; without crystallizing and separating, taking purewater as a reaction solvent and performing condensation on the pure water and aminothiazole acetyl chloride hydrochloride to form cefotiam; and performing hydrochloric acid acidification and crystallization on cefotiam to obtain cefotiam hydrochloride. A solvent used in the preparation method can be recycled, so that environment-friendly pressure is greatly reduced, environmental pollution is small, and indexes of cefotiam hydrochloride are improved while cost is reduced.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a new preparation method of an antibacterial drug cefotiam. Background technique [0002] Cefotiam hydrochloride chemical name: 7-[2-(2-aminothiazol-4-yl)acetamido]-[3-[[[(N,N)-dimethyl-amino-ethyl-tetrazolium -1-yl]thio]methyl]-8 oxo-5-thia-1-nitroxybicyclo[4,2,0]oct-2-ene-2-carboxylic acid]dihydrochloride as the second Substitution of cephalosporin antibiotics for injection. [0003] At present, the technology of this variety is mainly 7-aminocephalosporanic acid and 1-(2-dimethylaminoethyl)-1H-5-mercaptotetrazolium (MTZ) in acetonitrile solvent, using boron trifluoride complex Catalyze the synthesis of 7-ACMT, then add methanol and other solvents, drop triethylamine to adjust the pH crystallization, and centrifuge to obtain 7-ACMT solid, which is condensed with ATC.HCL in one or more mixed solvents to obtain cefotiam. Then acidify the crystal and centrifuge to obtain the cr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06
CPCC07D501/06C07D501/36
Inventor 于永宏刘明张义勋
Owner SHANGHAI NEW ASIA PHARMA
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