Aspoxicillin synthesis process

Abstract

The invention discloses an aspoxicillin synthesis process. The process comprises steps as follows: Dane salt (II) and an acyl chloride compound (III) react, a compound (IV) is obtained and reacts with amoxicillin (V), acid is added after the reaction ends, a salt forming product of aspoxicillin is obtained, and an aspoxicillin product is obtained after refining; the acid is selected from one or more of p-methyl benzenesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, fumaric acid, salicylic acid, citric acid, trifluoroacetic acid, oxalic acid and benzoic acid. The process is innovative, aftertreatment is not required in the whole reaction process, and the process has the characteristics that the operation is simple, the aftertreatment is convenient, the reaction period is shortened, the salt forming, washing, starching and impurity removal measures are added for an intermediate, few impurities are produced, the yield is high and the like and is suitable for industrial massive production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a new process for synthesizing apoxicillin. Background technique [0002] Apoxicillin, chemical name: (2S,5R,6R)-6-[(2R)-2-[(2R)-2-amino-3-(N-methylcarbamoyl)propionamide]-2- (p-Hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3,2,0]-heptane-2-carboxylic acid tris Hydrate, English name: Aspoxicillin Foreign trade name: Doyle Chinese pinyin name: APuXiLin, its structure is as follows: [0003] [0004] Apoxicillin is the world's first amino acid semi-synthetic penicillin drug for injection developed by Tanabe Pharmaceutical Company of Japan. It was first listed in Japan in 1987. Clinically, it can be used to treat sepsis, infective endocarditis, secondary infections of trauma, burns, surgical wounds, pharyngitis, tonsillitis, acute bronchitis, pneumonia, lung abscess, secondary infections of chronic respiratory diseases, Peritonitis, cholecy...

AI Technical Summary

Problems solved by technology

[0009] Aiming at the problem that the existing apoxicillin synthesis process is unstable, poor in repeatability and not suitable for industrial production, the present invention provides a process with simple operation, no need to use toxic reagents such as 2-nitrobenzenethiochloride, and high yield , the intermediate is easy to purify and operate, the product has high purity and less impurities, and is a new method for the synthesis of apoxicillin suitable for industrial production

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