Method for preparing 2-azabicyclo[2.2.1]heptyl-5-ene-3-one

Abstract

The invention discloses a preparation method of 2-azabicyclo(2.2.1)hept-5-alkene-3-ketone, which is an intermediate for the synthesis of antiviral medicine carbonyl ring nucleoside, which is characterized in that, an aqueous solution prepared by anhydrous sodium sulfite and sodium bicarbonate is added to a reactor; the temperature is controlled between 0 to 60 DEG C; a fixed amount of methanesulfonyl chloride is added by dropping, and the temperature is maintained to react for 2 to 4 hours to prepare methyl sulfonate solution; a fixed amount of ether solvent is added to the solution, and under a temperature ranging from 10 to 60 DEG C, cyanogens chloride is added; after 4 to 6 hours reaction, cyclopentadienyl is added by dropping; the pH value of the reaction solution is controlled between 1.5 to 3 to react for 3 to 5 hours; then sodium hydroxide is used for regulating the pH value to 7 to 9; after standing, the ether solvent is separated, and a fixed amount of methyl chloride is used for separated extraction 2-azabicyclo(2.2.1)hept-5-alkene-3-ketone; the methyl chloride is distilled and a crude product is obtained; the crude product is decolorized by activated carbon and recrystallized in ether solvent; 2-azabicyclo(2.2.1)hept-5-alkene-3-ketone with a purity of more than 99.6 percent is obtained after drying. The preparation method has the advantages of rich raw material sources, low cost, simple technological process, small emission of three wastes, benefits for industrial production and other advantages.

Description

Technical field [0001] The invention relates to the preparation of an intermediate for the synthesis of antiviral medicine carbonyl cyclic nucleosides, more specifically, it relates to the preparation of 2-azabicyclo[2.2.1]hept-5-en-3-one method. Background technique [0002] 2-Azabicyclo[2.2.1]hept-5-en-3-one is an intermediate in the synthesis of antiviral drugs carbonyl ring nucleosides. The carbonyl ring nucleoside has the function of substituting the oxygen atom in the furan ring constituting the nucleoside. Methyl substituted structure, because its structure is very similar to natural nucleosides, it can be used as a matrix, inhibitor, etc. of various enzymes in organisms. Because it does not have glycosidic bonds, it cannot be decomposed by phosphorylase, hydratase, etc. The metabolic pathway is different from the natural nucleoside, and it has a variety of physiological activities. For example, the bacterial metabolite carbonyl cyclic adenosine diphosphate is well known a...

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Problems solved by technology

[0008] 2. To decompose the intermediate, the excess of acetic acid must be 5 to 23 times, and at the same time, a large amount of heat will be generated, which will increase the reaction temperature, produce by-products, and reduce the yield;

[0009] 3. From the perspective of safety and economy, it cannot meet the requirements of industrialization

[0013] 1. The raw materials used are expensive, resulting in high product preparation costs;

[0014] 2. The intermediates of phenylsulfonyl cyanide and 2-azabicyclo[2.2.1]hept-5-en-3-one must be refined and purified step by step, resulting in complicated process;

[0015] 3. The content of the final product is 95%, which cannot meet the pharmaceutical requirements and is difficult to realize industrialization

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