Method for preparing 5-bromo-2-hydroxy-3-nitroacetophenone

Abstract

The present invention discloses a method for preparing 5-bromo-2-hydroxy-3-nitrophenylethanone. The method comprises that: (1) in the presence of an alkali, tetrachloroethylene is adopted as a reaction solvent, bromophenol completesly reacts with an acetylation reagent to obtain a tetrachloroethylene solution of bromoacetic acid phenolester; (2) Lewis acid is added to the resulting solution from the step (1) to completely carry out a Fries rearrangement reaction to obtain a tetrachloroethylene solution of 5-bromo-2-hydroxy acetophenone; (3) a nitration reagent is added to the resulting solution from the step (2) in a dropwise manner to completely carry out the reaction to obtain the 5-bromo-2-hydroxy-3-nitroacetophenone. According to the preparation method provided by the present invention, the three-step reaction is adopted, the tetrachloroethylenes having the same batch are adopted for purifying the final product, such that the solvent consuming is reduced, the cost is reduced, the post-processing time is shortened and the operation steps are simplified; the toxicity of the tetrachloroethylene is far less than the toxicities of chloroform and carbon tetrachloride, such that the hazards on the human body and the environment are less; the tetrachloroethylene is easy to reclaim; the industrialization is easy to realize.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, in particular to a method for preparing 5-bromo-2-hydroxyl-3-nitroacetophenone. Background technique [0002] 5-Bromo-2-hydroxy-3-nitroacetophenone is an important intermediate for the synthesis of pranlukast. Pranlukast is a leukotriene receptor antagonist developed by Japan Ono Company and listed in the mid-1990s, which has a good effect on the treatment of asthma. [0003] Asthma is a chronic respiratory disease characterized by varying degrees of reversible airway obstruction. Clinically commonly used β-receptor agonists and theophylline drugs can dilate the bronchi and relieve asthma symptoms, but they cannot effectively prevent the recurrent attacks of asthma, and long-term use will lead to drug resistance. Big side effects. Recent studies have made people gradually realize that chronic airway inflammation is the root cause of asthma attacks, so anti-i...

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Problems solved by technology

Similarly, the amount of solvent used is large and highly toxic, the process operation is cumbersome and dangerous, and the purity of the final product is not high

[0008] Patent CN101450943 uses tetrachloroethylene as the reaction solvent in the second step of the Fries rearrangement reaction, which greatly improves the rearrangement yield and reaction safety, but the first step of acetylation still uses chloroform as the solvent, and the third step still uses tetrachlorethylene. Carbon chloride is used as a solvent. At the same time, each step of the reaction needs to evaporate the solvent to obtain an intermediate, and then use a new batch of solvent for the next step. The amount of solvent is large, the toxicity is high, the reaction operation is cumbersome, the yield is low, and the energy consumption is high.

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