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Method for producing cefdinir active ester

A technology of cefdinir active ester and inert solvent, applied in the field of production of cefdinir active ester, can solve problems such as unqualified quality and low purity, and achieve the effects of reducing dosage, high product purity and few process steps

Pending Publication Date: 2021-04-16
SHANDONG JINCHENG KERUI CHEMICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] For the deficiencies in the prior art, the object of the present invention is to provide a kind of method of producing cefdinir active ester, organic base is used as hydrolysis agent and esterification catalyst simultaneously, avoids the low purity in the traditional technique, the situation of unqualified quality, The product of the invention has high purity, less waste water and waste salt, and the reaction solvent can be recycled and used mechanically, which is green and environmentally friendly

Method used

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  • Method for producing cefdinir active ester
  • Method for producing cefdinir active ester
  • Method for producing cefdinir active ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] At room temperature, add 20.16g of potassium tert-butoxide, 12.6g of tetramethylpropylenediamine and 400ml of acetonitrile into the three-necked flask, stir for 30min, throw in 50g of demethylaminothioxamic acid ethyl ester, stir for 4h, cool down to 25°C, and dropwise add 29.4g of acetic anhydride , with a pH value of about 6.1, reacted at 40°C for 1 hour to obtain an organic amine salt solution of acetylated demethylthioxamic acid;

[0042] Cool down to 15°C, add 23.0g triethyl phosphite dropwise, add 56.5g DM within 30min, keep warm for 1h, cool down to below 0°C, and filter with suction to obtain the crude cefdinir active ester;

[0043] The filter cake was dissolved in 200ml DMF, 360ml methanol was added dropwise for 1 hour, suction filtered, and vacuum-dried at 40°C for 4 hours to obtain 65.5g of cefdinir active ester with a molar yield of 74.02% and a purity of 99.45%. The HPLC data are shown in Table 1, and the spectrograms are shown in figure 1 .

[0044] Tab...

Embodiment 2

[0048] At room temperature, add 24.80g of potassium tert-butoxide, 18g of triethylamine and 400ml of acetonitrile into the three-necked flask, stir for 30min, throw in 50g of ethyl demethylaminothiaxate, stir for 4h, then cool down to 25°C and add 29.8g of acetic anhydride dropwise, the pH value is about 8.4, react at 40°C for 1 hour to obtain an organic amine salt solution of acetylated demethiazoxamic acid;

[0049] Cool down to 15°C, add 28.2g triethyl phosphite dropwise, add 56.8g DM within 60min, keep warm for 1h, cool down to below 0°C, and filter with suction to obtain the crude product of cefdinir active ester;

[0050] The filter cake was dissolved with 300ml DMF, 500ml methanol was added dropwise for 1 hour, suction filtered, and vacuum-dried at 40°C for 4 hours to obtain 60.1g of cefdinir active ester with a molar yield of 68.33% and a purity of 99.58%. The HPLC data are shown in Table 2, and the spectrograms are shown in figure 2 .

[0051] Table 2 Example 2 HPL...

Embodiment 3

[0054] At room temperature, add 13.9g of sodium methoxide, 16g of propylamine and 400ml of acetonitrile into the three-necked flask, stir for 30min, throw in 50g of ethyl demethylthioxamate, stir for 4h, then cool down to 25°C and add 30g of acetic anhydride dropwise, the pH value is about 5.2, at 40°C Reaction for 1h to obtain the organic amine salt solution of acetylated demethiazoxamic acid;

[0055]Cool down to 15°C, add 26.8g of triethyl phosphite dropwise, add 56.5g of DM within 90min, keep warm for 1h, cool down to below 0°C, and filter with suction to obtain the crude product of cefdinir active ester;

[0056] Dissolve the filter cake with 400ml of DMF, add 600ml of methanol dropwise for 1h, filter with suction, and dry in vacuum at 40°C for 4h to obtain 57.5g of cefdinir active ester with a molar yield of 65.48% and a purity of 99.59%. The HPLC data are shown in Table 3, and the spectrograms are shown in image 3 .

[0057] Table 3 Example 3 HPLC data sheet

[0058...

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Abstract

The invention relates to a method for producing cefdinir active ester, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps: by taking ethyl demethylaminothioxime acid as a raw material, dissolving the ethyl demethylaminothioxime acid by utilizing organic alkali and an inert solvent, reacting, cooling, adding acetic anhydride, and continuously reacting, so as to obtain an acetylated organic amine salt solution of the demethylaminothioxime acid; dropwise adding phosphite, and adding DM by controlling the feeding time to obtain a crude product; dissolving the crude product, and crystallizing to obtain the cefdinir active ester. According to the invention, the processes of aqueous-phase acid formation and crystal water removal in the traditional process are prevented, and no waste salt or waste water is generated; the organic base serves as a hydrolytic agent and an esterification catalyst, the use amount of the ester catalyst is reduced, and the cefdinir active ester with the purity of 99.40% or above can be obtained through a DMF / ROH elution method.

Description

technical field [0001] The invention relates to a method for producing cefdinir active ester, which belongs to the technical field of pharmaceutical synthesis. Background technique [0002] Cefdinir active ester, chemical name: S-2-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-acetoxyiminothioacetate, referred to as CAEM , the molecular formula is: C 14 h 10 o 3 N 4 S 3 , molecular weight: 378, CAS: 104797-47-9, its molecular structure is: [0003] [0004] Cefdinir is one of the important third-generation semi-synthetic cephalosporin antibiotics. It has strong bactericidal power, wide antibacterial spectrum, and is not easy to produce drug resistance. It has been widely used clinically and is the latest in the market. One of the oral cephalosporins. At present, 7-AVCA is generally synthesized by the active ester method, and the active ester mostly uses the cephalosporin side chain modified by mercaptobenzothiazole. [0005] Chinese patent CN105130925A discloses a ...

Claims

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Application Information

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IPC IPC(8): C07D277/74
Inventor 杜涵月贾万水刘明仁
Owner SHANDONG JINCHENG KERUI CHEMICAL CO LTD
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