Method for preparing cefixime

A cefixime and compound technology, applied in the field of pharmaceutical synthesis, can solve the problems of difficult drying, poor sulfate purity, low yield and the like, and achieve the effects of light appearance, avoiding inconvenience and high yield

Active Publication Date: 2005-11-16
天津市医药集团技术发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is disclosure in WO98 / 31685 again, during deprotection group reaction (99% formic acid), add a large amount of concentrated sulfuric acid to form cefixime sulfate and separate out, because by-product also forms salt with sulfuric acid and separates out, gained sulfate purity is poor, yield Low, difficult to filter, easy to absorb moisture, difficult to dry

Method used

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  • Method for preparing cefixime
  • Method for preparing cefixime
  • Method for preparing cefixime

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] In a 500ml reaction flask, add 7-[[(2-amino-4-thiazole)-[(tert-butyloxyacetyl)oxime]acetyl]amino]-3-vinyl-8-oxo-5-thia -15g of 1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid [III], 150ml of dichloromethane, 21ml of formic acid, 12ml of perchloric acid, heated to 30°C and kept stirring for 2 hours. Cool down to below 5°C, precipitate a solid, filter, and dry to give light yellow 7-[[(2-amino-4-thiazole)-[(carboxymethyl)oxime]acetyl]amino]-3-vinyl-8-oxo - 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid perchlorate [I] 16.5 g, yield 91.7%, HPLC 98%. 1 H-NMR (DMSO): 3.6, 3.8 (ABq, 2H), 4.69 (s, 2H), 5.20 (d, 1H), 5.31 (d, 1H), 5.59 (d, 1H), 5.79 (dd, 1H) , 6.92 (dd, 1H), 6.99 (s, 1H), 9.71 (d, 1H).

Embodiment 2

[0026] In a 500ml reaction flask, add 7-[[(2-amino-4-thiazole)-[(tert-butyloxyacetyl)oxime]acetyl]amino]-3-vinyl-8-oxo-5-thia -1-Azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid [III] 5g, ethyl acetate 100ml, formic acid 3ml, perchloric acid 2ml, heat up to 40°C and keep stirring for 1 hour. Cool down to below 5°C, precipitate a solid, filter, and dry to give light yellow 7-[[(2-amino-4-thiazole)-[(carboxymethyl)oxime]acetyl]amino]-3-vinyl-8-oxo -5.2 g of 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid perchlorate [I], yield 87%, HPLC 98.2%. 1 H-NMR (DMSO): 3.6, 3.8 (ABq, 2H), 4.69 (s, 2H), 5.20 (d, 1H), 5.31 (d, 1H), 5.59 (d, 1H), 5.79 (dd, 1H) , 6.92 (dd, 1H), 6.99 (s, 1H), 9.71 (d, 1H).

Embodiment 3

[0028] In a 500ml reaction flask, 7-[[(2-amino-4-thiazole)-[(carboxymethyl)oxime]acetyl]amino]-3-vinyl-8-oxo-5-thia-1 -Azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid perchlorate [I]16g was suspended in 150ml of water, the temperature was lowered to below 5°C, a saturated solution of sodium carbonate was added dropwise, and the solid was stirred and dissolved Afterwards, add carbon to decolorize for 1 hour. Filtrate, adjust the filtrate to pH 2.5 with 4N hydrochloric acid, stir at 5°C for 0.5 hours, filter out the solid, and dry to obtain 7-[[(2-amino-4-thiazole)-[(carboxymethyl)oxime]acetyl]amino 12 g of ]-3-vinyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (II, cefixime). HPLC 98.3%

[0029] 1 H-NMR (DMSO-D6): 3.54, 3.8 (ABq, 2H), 4.58 (s, 2H), 5.20 (d, 1H), 5.31 (d, 1H), 5.59 (d, 1H), 5.80 (dd, 1H), 6.80 (s, 2H), 6.86 (dd, 2H), 7.24 (s, 2H), 9.54 (d, 1H).

[0030] IR: 3536cm -1 , 3297cm -1 , 2948cm -1 , 3300-2500cm -1 , 1771cm -1 , 1668cm -1 , 1096cm...

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Abstract

A process for preparingcefixime from perhalate includes reaction between compound A, perhalognic acid and organic protonic acid to obtain cefixime perhalate, removing protective radical, and setting free.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and relates to the synthesis of cephalosporins, more specifically, a preparation method of the third-generation oral cephalosporin cefixime. Background technique [0002] Cefixime (II), chemical name: (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido]- 8-Oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid trihydrate is a semi-synthetic third-generation oral cephalosporin with Both Gram-positive bacteria and Gram-negative bacteria have strong antibacterial effect and are highly stable to β-lactamase. [0003] According to literature reports, cefixime is generally prepared by the following synthetic method. [0004] [0005] where R 1 For hydrogen or carboxyl protecting group p-methoxybenzyl, benzhydryl, etc., R 2 It is a lower aliphatic hydrocarbon group such as carboxyl protecting group methyl, tert-butyl, etc. Z is chlorine or mercaptobenzoth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/22
Inventor 周永健孟红赵平边颖蔡毅李玉荃
Owner 天津市医药集团技术发展有限公司
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