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Intermediate for preparing carbapenem antibiotics and preparation method thereof

A technology for carbapenems and antibiotics, which is applied in the field of intermediates for preparing carbapenem antibiotics, can solve the problems of harsh reaction conditions, long synthesis routes, rare raw materials, etc., and achieves short synthesis routes, low cost, and raw materials. easy-to-get effect

Inactive Publication Date: 2011-12-07
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, this type of antibiotics is mainly prepared by chemical total synthesis, but the existing preparation methods are not completely satisfactory, and there are problems such as long synthetic routes, rare raw materials, harsh reaction conditions, low yields, and high costs.

Method used

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  • Intermediate for preparing carbapenem antibiotics and preparation method thereof
  • Intermediate for preparing carbapenem antibiotics and preparation method thereof
  • Intermediate for preparing carbapenem antibiotics and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1, the preparation of intermediate

[0026] 1. Preparation of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsiloxy)ethyl]-4-allyl-2-azetidinone (II)

[0027] Take 16g of zinc powder, add 40mL of hydrochloric acid solution with a concentration of 0.6mol / L, soak for 5 minutes, suction filtration, the filter cake is washed with absolute ethanol, acetone, and anhydrous ether in turn, and then dried at a temperature of 110 ° C under vacuum conditions for 40 minutes. minutes, and then cooled to room temperature under vacuum conditions to obtain activated zinc powder, which was stored under nitrogen protection for future use;

[0028] Calculate the amount of raw materials according to the theoretical yield of the product 18.7g; dissolve compound I 20g (70mmol) in 160mL of anhydrous tetrahydrofuran (THF), under nitrogen protection, add 14g (215mmol) of activated zinc powder, and then at a temperature of 32 ℃ 12.4 mL (140 mmol) of allyl bromide was slowly added dropwise, and ...

Embodiment 2

[0040] Embodiment 2, the preparation of intermediate

[0041] 1. Preparation of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsiloxy)ethyl]-4-allyl-2-azetidinone (II)

[0042] The preparation method of activated zinc powder is the same as the method described in Example 1;

[0043] Calculate the amount of raw materials according to the theoretical product yield of 18.7g; dissolve 20g (70mmol) of compound I in 160mL of anhydrous N,N-dimethylformamide (DMF), under nitrogen protection, add 14g (215mmol) of activated zinc powder ), then slowly drip allyl bromide 18.6mL (210mmol) under the condition of temperature 32 ℃, after the completion of the dropwise addition, the reaction was stirred under nitrogen protection and room temperature for 3 hours, suction filtration, and the filtrate was cooled to a temperature of 10~15 ℃, Add 0.8 mol / L hydrochloric acid solution until the mixture becomes clear, add ethyl acetate for extraction, wash the extract with saturated sodium chloride solution, d...

Embodiment 3

[0050] Embodiment 3, the preparation of intermediate

[0051] 1. Preparation of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsiloxy)ethyl]-4-allyl-2-azetidinone (II)

[0052] The preparation method of activated zinc powder is the same as the method described in Example 1;

[0053] Calculate the amount of raw materials according to the theoretical yield of the product 18.7g; dissolve compound I 20g (70mmol) in 160mL of anhydrous THF, under nitrogen protection, add 14g (215mmol) of activated zinc powder, and then slowly add dropwise at a temperature of 30°C Allyl bromide 6.2mL (70mmol), after the dropwise addition, the reaction was stirred under nitrogen protection and room temperature for 2 hours, suction filtered, the filtrate was cooled to a temperature of 10 to 15°C, and a hydrochloric acid solution with a concentration of 0.8mol / L was added to mix. The liquid became clear, ethyl acetate was added for extraction, the extract was washed with saturated sodium chloride solution, dried...

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Abstract

The invention discloses an intermediate for preparing carbapenem antibiotics, which has the following structural formula: wherein, TBDMS is tert-butyldimethylsilyl, Boc is tert-butoxycarbonyl; the chemical name is (3S, 4R )-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-{2-[2-(tert-butoxycarbonylamino)ethylthio]carboxyethyl}- 2-azetidinone; the present invention also discloses the preparation method of the intermediate, using 4-acetoxy-2-azetidinone as the starting material, including allylation reaction, oxidation reaction, ester The chemical reaction consists of 3 steps; the preparation method of the present invention has short synthesis route, easy-to-obtain raw materials, no need for special and expensive reagents, mild reaction conditions, easy separation and purification of products, high yield and low cost, and is suitable for industrial production.

Description

technical field [0001] The present invention relates to a compound, in particular to an intermediate for preparing carbapenem antibiotics, and a preparation method of the intermediate. Background technique [0002] The β-lactamase produced by bacteria hydrolyzes the skeleton structure of typical β-lactam antibiotics such as penicillin and cephalosporin, so that it loses its antibacterial activity, which is the main mechanism of bacterial resistance. Carbapenems are both atypical β-lactam antibiotics and β-lactamase inhibitors, with broad antibacterial spectrum, strong antibacterial activity, rapid action, and high stability to most β-lactamases The characteristics of β-lactam antibiotics are one of the important directions in the field of β-lactam antibiotic research. Thienamycin derivatives, which have been used in clinical practice, are widely used in the treatment of severe infections caused by unknown pathogens. [0003] The research on the chemical synthesis of carbape...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F7/18C07D205/08
Inventor 夏之宁李春燕穆小静蒋宏贵
Owner CHONGQING UNIV