Preparation method of bromoacetonitrile

Abstract

The invention relates to a preparation method of bromoacetonitrile in the technical field of medicine production, which comprises the following steps: reacting cyanomethanesulfonate with brominated salt, and carrying out reactive distillation to obtain a crude product; and rectifying to obtain bromoacetonitrile. According to the present situation that the product quality of the original process is poor, and the crude product contains about 5% of hydroxyacetonitrile, the process of removing water in the reaction system is adopted, so that the generation of hydroxyacetonitrile is avoided, and the rectification efficiency is improved. The novel preparation method provided by the invention overcomes the defects of the existing process, has the advantages of short reaction time, high product purity, high yield and the like, and is suitable for industrial amplification.

Description

technical field [0001] The invention relates to a preparation method of bromoacetonitrile, and belongs to the technical field of pharmaceutical production. Background technique [0002] The English name of bromoacetonitrile is: cyanomethyl bromide, bromoacetonitrile; CAS#: 590-17-0; boiling point 60-62 °C / 24 mmHg (lit.) , 150 - 151 °C / 752mmHg; density 1.722 g / mL at 25 °C(lit.) [0003] The structure is as follows: [0004] [0005] Bromoacetonitrile is a very useful synthetic intermediate, especially widely used in the production process of new drugs. Example 1: The synthetic fragment of the new crown drug: [0006] [0007] Its intermediate: [0008] [0009] Preparation method of (S)-2-(BOC-amino)-3-[(S)-2-oxo-3-pyrrolidinyl]propionic acid methyl ester (CAS RegistryNumber(s): 328086-60-8) . [0010] Example 2: A synthetic fragment of a new anticancer drug: [0011] The following intermediates were synthesized using bromoacetonitrile: [0012] [0013] 6...

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Problems solved by technology

[0021] The route is a process route commonly used in China at present, but the reaction time of the raw material chloroacetonitrile is long, and the moisture in the reaction system causes the hydrolysis of bromoacetonitrile to hydroxyacetonitrile, etc., resulting in low content of the obtained product; additional measures need to be taken to obtain qualified The product

The post-treatment of Chinese patent CN113582874 adopts filtration to remove the solid in the reaction system. It is well known that chloroacetonitrile and bromoacetonitrile have strong irritation, and the working environment is poor; the solid contains a large amount of products, which requires multiple solvent washings, resulting in cumbersome production operations. At the same time, the solvents acetone and methanol are flammable and explosive solvents, which have great potential safety hazards; in addition, a large amount of waste residue produced in production contains a small amount of chloroacetonitrile, bromoacetonitrile and hydroxyacetonitrile, which are difficult to handle, which is extremely serious for environmental pollution.

[0030] Add solid phosphorus pentoxide to 2-bromoacetamide, heat and dehydrate, and steam bromoacetonitrile while heating, because the reaction is to remove a part of water, it is easy to produce hydrolyzed impurities; from the perspective of environmental protection, the three wastes of phosphorus pentoxide Large, not suitable for mass production

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