4-hydroxyindole preparation method suitable for industrial production

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of a medical intermediate 4-hydroxyindole. The method includes: taking 1, 5, 6, 7-tetrahydro-4H-indole-4-one as the raw material, carrying out nucleophilic substitution reaction under the action of alkali to obtain an amino protection product (I), reacting the compound (I) with a halogenation reagent to obtain alpha-halogenated ketone (II), subjecting the compound (II) to elimination reaction under the action of alkali to remove HX so as to obtain a 4-hydroxyindole derivative (III), and finally conducting hydrolysis deprotection on the compound (III) to obtain 4-hydroxyindole (IV). The invention provides a simple industrial production route for 4-hydroxyindole, and the method has the advantages of simple reaction operation, avoidance of high temperature, high pressure and catalytic reaction, and low cost.

Description

Technical field [0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a preparation method of 4-hydroxyindole suitable for industrial production. Background technique [0002] Hydroxyindoles are raw materials for the synthesis of many natural compounds. Among the many discovered natural products and pharmaceutically active compounds, indole often serves as a significant structural unit. Therefore, it is necessary to obtain new synthesis of this skeleton with different substitution forms. Methods are the main goal of current organic synthesis. [0003] Indole derivatives such as hydroxyindole are also important organic chemical raw materials and pharmaceutical intermediates. They can be used to synthesize dyes, spices and some drugs, and can also be used as plant auxins, feed additives, etc. In particular, 4-hydroxyindole is an important intermediate in the synthesis of the angina treatment drug Pindolol (Pindolol) and the psyc...

AI Technical Summary

Problems solved by technology

[0006] The disadvantage of this route is that the starting material 2,6-dinitrotoluene is a controlled explosive, and the reaction requires expensive palladium reagent, and high temperature (220° C.) and high pressure are required in the reaction process, and the conditions are relatively harsh, so it cannot Realize industrial production

[0009] The disadvantage of this route is that the reaction steps are longer and the reaction time is longer, the starting material 2,6-dinitrotoluene is a controlled explosive, and the formylation raw material methyl chloroformate is a highly toxic drug, which is prohibited from sale. Unable to achieve industrial production

[0012] The shortcoming of this route is: overall yield is lower, and starting raw material price is more expensive, and reaction time is long, wherein has two steps to use expensive palladium catalyst, is unfavorable for suitability for industrialized production

[0015] The disadvantage of this route is that the yield of the first step is low, the step of closing the ring requires high pressure, and the conditions are relatively harsh, and both steps use expensive palladium reagent, which has high cost and is not conducive to industrial production.

[0018] The disadvantage of this route is that it needs to be operated under high pressure, the reaction conditions are relatively harsh, the equipment requirements are high, and expensive palladium reagents and platinum reagents are used, which is not conducive to industrial production

[0021] The disadvantage of this route is that the price of starting raw materials is relatively high, and high-pressure reaction and expensive palladium reagent are also required, which is not conducive to industrial production

[0024] The disadvantage of this route is that: the palladium reagent is also used, the post-treatment is complicated, and the reaction temperature is too high, which is not conducive to industrial production

[0026] As can be seen from the 7 methods of 4-oxindole reported in the above literature, some have high reaction temperature, harsh reaction conditions, some use more expensive catalysts, some have long reaction routes, and have low yields. There are certain defects in production

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