Method for preparing 7-ACCA

A technology for controlling temperature and phenylacetamide, applied in the field of preparation of 7-ACCA

Inactive Publication Date: 2011-10-19
ZHANGJIAGANG XINYI CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0015] The technical problem to be solved by the present invention is to overcome the above-mentioned shortcoming and deficie

Method used

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  • Method for preparing 7-ACCA
  • Method for preparing 7-ACCA
  • Method for preparing 7-ACCA

Examples

Experimental program
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Embodiment 1

[0031] 1) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester:

[0032] Take 400g of chloroform, 68g of triphosgene (triphosgene, chemical name, bis(trichloromethyl)carbonate, referred to as BTC), 72g of DMF, control the temperature at 0±1°C, stir for 2 hours, add 60g 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester, controlled temperature 55±2°C, stirred and reacted for 10 hours, and slowly poured into 150g (10 %, mass percentage concentration) in NaOH solution, control pH 12~13, control temperature 25 ± 2 ℃, stir reaction for 1 hour, stand still, separate layers, distill off chloroform under reduced pressure, add methanol 150g, cool and crystallize, filter, After washing and drying, 54.7 g of p-nitrobenzyl 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylate was obtained, with a purity of more than 98%;

[0033] 2) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid:

...

Embodiment 2

[0038] 1) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester:

[0039] Take 5000g of chloroform, 800g of triphosgene (triphosgene, chemical name, bis(trichloromethyl)carbonate, referred to as BTC), 1000g of DMF, control the temperature at 0±1°C, stir for 3 hours, add 600g 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester, controlled temperature 55±2°C, stirred and reacted for 12 hours, and slowly poured into 2000g (10 %, mass percentage concentration) in NaOH solution, control pH 12~13, control temperature 25 ± 2 ℃, stir reaction for 1 hour, stand still, separate layers, distill off chloroform under reduced pressure, add methanol 2000g, cool and crystallize, filter, Washing and drying to obtain 550 g of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester product with a purity of more than 98%;

[0040] 2) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carbox...

Embodiment 3

[0045] 1) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester:

[0046] Take 2000g of chloroform, 430g of triphosgene (triphosgene, chemical name, bis(trichloromethyl)carbonate, referred to as BTC), 450g of DMF, control the temperature at 0±1°C, stir for 3 hours, add 300g 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester, controlled temperature 55±2°C, stirred and reacted for 12 hours, and slowly poured into 1000g (10 %, mass percent concentration) in NaOH solution, control pH 12~13, control temperature 25 ± 2 ℃, stir reaction for 1 hour, stand still, separate layers, distill off chloroform under reduced pressure, add methanol 700g, cool and crystallize, filter, After washing and drying, 270 g of p-nitrobenzyl 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylate was obtained, with a purity of more than 98%;

[0047] 2) Preparation of 7-phenylacetamido-3-chloro-3-cephalosporin-4-carboxylic acid: ...

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Abstract

The invention relates to an important intermediate 7-ACCA of cephalosporin cefaclor, comprising the following steps of: 1) preparation of 3-amino-2-ethoxyformyl anesthesin; 2) preparation of 2-ethoxybenzimidazole-4-carboxylic acid ethyl ester; 3) preparation of candesartan cyclic compound. According to the invention, the benzimidazole ring is constructed, tetraehtyl orthocarbonate is avoided, andintramolecular dehydration is accomplished; and alkylation is accomplished in the final stage and cyanobromobiphenyl is introduced to minimize the consumption of cyanobromobiphenyl as well as the cost of the candesartan cyclic compound.

Description

technical field [0001] The invention relates to a preparation method of an important intermediate 7-ACCA of the cephalosporin cefaclor. Background technique [0002] Cefaclor is a widely used broad-spectrum antimicrobial drug. Among the marketed drugs, it has a good curative effect and the market has achieved unprecedented development. The key to the synthesis of the drug is the preparation of the intermediate 7-ACCA. [0003] 7-ACCA chemical name: 7-amino-3-chloro-3-cephalosporin-4-carboxylic acid [0004] The structural formula is as follows: [0005] [0006] At present, the common methods for the synthesis of 7-ACCA can be summarized into two types: A and B: [0007] A kind of is the route that is raw material with 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid diphenylmethyl ester, at first by the chlorination of phosphorus oxychloride, makes 7-phenylacetamido -3-Chloro-3-cephalosporin-4-carboxylic acid diphenylmethyl ester; after the elimination ...

Claims

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Application Information

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IPC IPC(8): C12P35/02
Inventor 楼新灿陈立坤
Owner ZHANGJIAGANG XINYI CHEM
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