A kind of mirtazapine synthesis and aftertreatment method

Abstract

The invention discloses a method for synthesizing and post-processing mirtazapine, comprising: (1) putting mirtazapine into concentrated sulfuric acid in batches, and stirring at 20-30 DEG C for 8-16 hours; (2) under stirring conditions, adding The above-mentioned vitriol oil reaction solution is dropped into the mixture of ice and methyl tertiary butyl ether, and keeps reflux condensation; (3) in above-mentioned mixed solution, add sodium hydroxide solution, make the pH of aqueous solution layer be greater than 11, and keep reflux condensation; ( 4) The above mixed solution is evaporated under reduced pressure to remove the methyl tert-butyl ether solvent to obtain a crude mirtazapine product. The method for synthesizing and post-processing mirtazapine provided by the invention adopts methyl tert-butyl ether as the extraction solvent, and even if concentrated sulfuric acid and sodium hydroxide are added rapidly, the temperature can be effectively controlled, thereby controlling the generation of impurities and improving the production efficiency.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a synthesis and post-treatment method of mirtazapine. Background technique [0002] Mirtazapine (English name is mirtazapine, compound Ⅰ) is an effective antidepressant drug (US4062848), it is a selective serotonin reuptake inhibitor, this drug was developed by the Organon company in the United States, and was first released in 1994 Marketed in the Netherlands, it was approved by the US FDA in 1996 and has been widely used clinically in many countries around the world. [0003] The synthetic reaction formula of mirtazapine is as follows figure 1 As shown, mirtazapine removes a molecule of water in concentrated sulfuric acid, and cyclizes to form mirtazapine. After post-treatment to remove impurities, the crude product is obtained, and then refined to obtain the finished product. The specific synthesis process of existing mirtazapine is: put mirtazapine (100g) into concentrated...

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Problems solved by technology

[0004] However, in the existing process, both dilute concentrated sulfuric acid and neutralized sulfuric acid are used to control the temperature by dropping, which is inefficient in the scale-up production process; and toluene is used as the extraction solvent, which needs to be heated to 80°C, resulting in material degradation and a large amount of impurities; Therefore, it is necessary to adopt the recrystallization process for purification, and finally the mother liquor is directly scrapped, which directly affects the yield, which is not economical nor environmentally friendly

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