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Synthesis method of ertapenem sodium

A technology of ertapenem sodium and its synthesis method, which is applied in the field of drug synthesis and can solve the problems of poor purity, small production capacity, and high residues of heavy metals in products

Active Publication Date: 2022-03-01
SHENZHEN HAIBIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In view of this, the present application provides a synthesis method of ertapenem sodium, which effectively solves the existing ertapenem synthesis methods that require cumbersome post-processing, low production capacity, high heavy metal residues in the product, and poor purity. technical problem

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  • Synthesis method of ertapenem sodium
  • Synthesis method of ertapenem sodium
  • Synthesis method of ertapenem sodium

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Embodiment 1

[0040] The embodiment of the present application provides the preparation method of the compound shown in formula 1, specifically including:

[0041] According to the following synthetic route, dissolve 94.2g of carbapenem core MAP and 57.3g of ertapenem side chain hydrochloride in 600g of DMF, add 60.8g of tetramethylguanidine dropwise at -50°C, and stir Condensation reaction, after the reaction is completed, the pH value of phosphoric acid is adjusted to 5, and the acid-adjusted feed solution is added to water for crystallization to obtain a compound represented by formula 1 as a solid. Its purity is 98.9%.

[0042] .

Embodiment 2

[0044] The embodiment of the present application provides the preparation method of ertapenem sodium, which specifically includes:

[0045] Add 93g of water, 50g of methanol, 24g of n-propanol, 53g of ethyl acetate, 10g of the compound shown in formula 1, 4.2g of sodium bicarbonate into the three-necked flask, stir and dissolve, add to the hydrogenation kettle, and simultaneously add 1.13g of palladium carbon, Replace with nitrogen, add hydrogen to 2.0Mpa, react at 20°C for 3 hours, after the reaction is completed, filter, separate liquids to obtain a product solution, use aqueous hydrochloric acid to adjust the pH value of the product solution to 6.0, add an equal volume of methanol and n-propanol to carry out After crystallization and drying, 6.7 g of white ertapenem sodium solid was obtained, with a molar yield of 82.1%, an HPLC purity of 99.09%, and a heavy metal content of <10 ppm.

[0046] Measure the chromatogram of the ertapenem sodium that the embodiment of the presen...

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Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of ertapenem sodium. The invention provides a synthesis method of ertapenem sodium, which comprises the following steps: in the presence of alkali, a catalyst and a hydrogen atmosphere, mixing a compound as shown in a formula 1 with a mixed solvent for hydrogenation reaction, filtering to obtain a product solution, extracting and purifying with ethyl acetate, and adjusting the pH value of a water phase to 4-7 to obtain an acidic product solution; adding a crystal forcing solvent into the acidic product solution for crystallization to obtain ertapenem sodium; the ertapenem sodium has a structure as shown in a formula 2. The invention provides a synthesis method of ertapenem sodium, and effectively solves the technical problems of need of tedious post-treatment, low productivity, high product heavy metal residue and poor purity in the existing synthesis method of ertapenem.

Description

technical field [0001] The application belongs to the technical field of pharmaceutical synthesis, and in particular relates to a synthesis method of ertapenem sodium. Background technique [0002] Ertapenem (Ertapenem, structural formula is ) is a carbapenem antibiotic with broad-spectrum antibacterial properties, jointly developed by Merck and AstraZeneca, its chemical name is (4R, 5R, 6S)-6-[(3S,5S)- 5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-nitrogen Heterobicyclo[3.2.0]hept-2-ene-2-carboxylic acid. [0003] At present, the mainstream method for industrial production of penem compounds is: hydrogenation of palladium carbon followed by deprotection, and ertapenem is also used for hydrogenation and deprotection. However, deprotection using this method faces a problem of excessive heavy metals. At the same time, due to the instability of ertapenem itself, the cumbersome post-processing operation makes the product seriousl...

Claims

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Application Information

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IPC IPC(8): C07D477/08C07D477/20
CPCC07D477/08C07D477/20
Inventor 姜能江林楠棋欧军王东幸志伟孙万鹏
Owner SHENZHEN HAIBIN PHARMA
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