Preparation method of amikacin

Abstract

The invention discloses a preparation method of amikacin, belonging to the technical field of medicines. In a silylation reaction process, ammonium sulfate is micronized to remove a commonly-used solvent, hexamethyl disilazane is not only used as a reactant, but also used as a solvent, reaction time is shortened to about 2 hours, materials are easy to operate, and the preparation method is environment-friendly. Besides, in the silylation reaction process, a divalent metal organic weak acid salt is used as a complexing agent, so that the silylation reaction time can be shorted to about 1 hour; and meanwhile, selectivity of subsequent acylation reaction is improved, and yield of synthesizing the amikacin is improved.

Description

technical field [0001] The invention relates to a preparation method of amikacin, which belongs to the technical field of medicine. Background technique [0002] Amikacin sulfate is a semi-synthetic aminoglycoside antibiotic with a broad antibacterial spectrum and strong antibacterial ability against a variety of bacteria. Since its launch in the 1970s, amikacin sulfate has been widely used due to its definite curative effect, and has become the first-line anti-infective drug commonly used clinically in the world. In my country, Amikacin Sulfate has been included in the National Essential Drug List, and also included in the Class A drug in the "National Basic Medical Insurance and Work Injury Insurance Drug List". [0003] Amikacin, also known as amikacin. The most commonly used amikacin synthetic route is the silanization protection route (Jiang Zhongliang, Wang Yu. A new synthetic method of amikacin [J], Fine and Specialty Chemicals, 2004, 12 (10 ), 26-28). Specificall...

AI Technical Summary

Problems solved by technology

Due to the poor activity of the commonly used catalysts, a large amount of flammable, explosive, and volatile solvents are required for the dissolution reaction. The use of solvents in the process is relatively large, and they are volatile, resulting in large losses, affecting the environment, and increasing costs.

Kanamycin sulfate has the disadvantages of low catalytic activity and slow catalytic silicification reaction, which usually takes about 28 hours and is not suitable for industrial production

Another commonly used catalyst, trimethylchlorosilane, has the following disadvantages, although its time is relatively short: (1) it is liquid at room temperature, and it is easy to absorb water in the air and undergo hydrolysis to release hydrogen chloride. On the one hand, it pollutes the environment and on the other hand On the one hand, it affects the health of people

(2) Hydrogen chloride gas generated by volatilization and water absorption is easy to corrode equipment

(3) Ammonium chloride solid is produced during the reflux reaction, and it is attached to the condenser during the reflux process, which affects the condensation effect. The condenser needs to be cleaned regularly, because the reaction is an anhydrous reaction, so a large amount of solvent is required after cleaning Carry out water, increase the consumption cost of solvent

[0008] The yield of the silanization reaction in the document US4424343 is low, the yield is about 90% (calculated according to the full protection), and there is still a large room for improvement in the yield

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