Environmentally-friendly synthesis process of Aztreonam main ring (3S-trans)-3-amino-4-methyl-2-oxo-1-azetidinyl sulfonic acid

A kind of technology of azetidine sulfonic acid, main ring of aztreonam, applied in main ring of aztreonam (3S-trans)-3-amino-4-methyl-2-oxo-1-nitrogen The field of environmental protection synthesis technology of hexacyclobutanesulfonic acid can solve the problems of inconvenient operation, high production cost, troublesome post-processing, etc., and achieve the effects of eliminating recovery operation, low production cost, and simple post-processing.

Inactive Publication Date: 2012-03-21
CHONGQING NANSONG CHEMI TECH +1
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Problems solved by technology

[0004] Method 1: A large amount of thionyl chloride (80 grams of L-threonine, 165 ml of thionyl chloride) is used for esterification, which produces a large amount of hydrogen chloride and sulfur dioxide, which are toxic and harmful gases; Cbz (benzyloxyformyl) amino Protection, palladium-carbon catalytic hydrogenation deprotection is needed later, palladium-carbon catalyst is expensive, the production cost is high, the organic solvent used in the whole process is more, the amount is larger, post-processing is troublesome, and the total

Method used

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Examples

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Embodiment 1

[0020] 1, Synthesis of L-Threonine Methyl Hydrogen Sulfate

[0021] Add 80 grams of L-threonine and 240 grams of methanol into the reactor, stir at room temperature, add 96 grams of concentrated sulfuric acid dropwise, control the temperature not to exceed about 45°C, after the dropwise addition, heat to about 45°C for 24 hours, TLC (Thin-layer chromatography) showed that the reaction was complete, and a methanol solution of L-threonine methyl bisulfate was obtained.

[0022] 2. Synthesis of L-threonine amide:

[0023] Add the methanol solution of L-threonine methyl ester bisulfate obtained in the previous step to the reactor, stir at room temperature, pass ammonia until TLC shows that the reaction is complete, filter with suction, and evaporate the filtrate to dryness (recover methanol) to obtain L-threonine Aminoamide.

[0024] 3. Synthesis of N-BOC-L-threonine amide:

[0025] In the reactor, add the L-threonine amide obtained in the previous step, 300 grams of wat...

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Abstract

The invention provides an environmentally-friendly synthesis process of Aztreonam main ring (3S-trans)-3-amino-4-methyl-2-oxo-1-azetidinyl sulfonic acid. The synthesis process comprises: carrying out methyl esterification on L-threonine, carrying out ammonolysis on L-threonine methyl ester bisulfate, carrying out N-BOC (N-tert-butoxycarbonyl) protection on amino group of L-threoninamide, carrying out mesylation on N-BOC-L-threoninamide, carrying out sulfonylation on N-BOC-O-mesyl-L-threoninamide, carrying out cyclization reaction on sodium N-BOC-O-mesyl-L-threoninamide sulfonate, and de-protecting and acidifying sodium (3S-trans)-3-tert-butoxyformamido-4-methyl-2-oxo-1-azetidinyl sulfonate to obtain (3S-trans)-3-amino-4-methyl-2-oxo-1-azetidinyl sulfonic acid. The synthesis process has the advantages that simple post-treatment, high yield, high utilization rate of wastes, low cost and low pollution; moreover raw materials can be obtained easily.

Description

technical field [0001] The invention relates to an environment-friendly synthesis process of the main ring (3S-trans)-3-amino-4-methyl-2-oxo-1-azetidinesulfonic acid of the antibiotic medicine aztreonam. Background technique [0002] Aztreonam is the first synthetic monocyclic β-lactam antibiotic developed by Bristol-Myers Squibb Co. It has a good therapeutic effect on Gram-negative bacterial infections, such as pneumonia, Pleurisy, abdominal infection, biliary tract infection, bone and joint infection, etc., especially for urinary tract infection. And its cost largely depends on the production cost of its main ring. The existing methods for synthesizing the main ring mainly include: 1. Starting from L-threonine, through esterification, ammonolysis, Cbz (benzyloxyformyl) amino protection, hydroxyl protection, sulfonation, cyclization, and deprotection reactions The obtained (3S-trans)-3-amino-4-methyl-2-oxo-1-azetidine sulfonic acid {Zhang Hong et al. Study on the synthesi...

Claims

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Application Information

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IPC IPC(8): C07D205/085
Inventor 衡林森高兴华伦前万新波张练赵海
Owner CHONGQING NANSONG CHEMI TECH
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