A kind of efficient preparation method of doxycycline

Abstract

The invention discloses a high-efficiency preparation method of doxycycline, and belongs to the technical field of medicine synthesizing. The high-efficiency preparation method of doxycycline is technically characterized in that the specific synthesizing route is shown in the description. The high-efficiency preparation method has the advantages that the cost of raw materials is low, the obtaining is easy, the technology operation is simple, the repeatability is good, and the yield rate is relatively high.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical synthesis, and in particular relates to a high-efficiency preparation method of doxycycline. Background technique [0002] Antibiotics are the most extensive class of antibacterial drugs. In the early 1940s, the clinical application of penicillin G promoted the improvement of antibacterial drugs and accelerated the development of antibacterial drugs. Antibiotics, formerly known as antibiotics, are secondary metabolites or synthetic analogues of microorganisms, which can inhibit the growth and survival of microorganisms in vitro without causing serious toxic side effects on host cells. In clinical treatment, most antibiotics can inhibit bacterial infection and are used for the prevention and treatment of bacterial infectious diseases. In fact, it can not only kill viruses and bacteria, but also have good inhibitory and inactivation effects on mold, mycoplasma, chlamydia and other microorga...

AI Technical Summary

Problems solved by technology

[0007] 1. Hydrofluoric acid dehydration: Hydrofluoric acid is slowly corrosive to the environment, equipment and operators during use, so the safety of production operations is low and it is harmful to the human body;

[0008] 2. Dechlorination and hydrogenation: Palladium carbon dechlorination and hydrogenation process has poor isomer selectivity. After dechlorination and hydrogenation, a mixture of a configuration and b configuration isomer is obtained. The target product is a configuration isomer. The content of b isomer is required to be less than 2%, but after dechlorination and hydrogenation, the yield of a configuration is only about 75%, and the ee value is less than 60%;

[0009] 3. Salt conversion: the original process utilizes the strong binding force of a configuration and sulfosalicylic acid to convert p-toluenesulfonate into sulfosalicylate to increase the ratio of a configuration, but it will lead to sulfonic acid in the reaction mother liquor There are a large amount of acids such as salicylic acid and p-toluenesulfonic acid, if not treated, it will cause great environmental pollution, there are literature reports that can be treated, but the cost of treatment is high, and it is difficult to realize industrialization, so a considerable part of the production Business shut down due to this issue

[0010] Therefore, the original synthesis process of doxycycline has problems such as harsh production conditions, low yield of a isomer and ee value, high cost and large environmental pollution.