Chlorzoxazone synthesis method

Abstract

The invention belongs to the technical field of medicine synthesis, and provides a novel chlorzoxazone synthesis method which comprises the following steps: carrying out ring expansion reaction on a raw material SM-1 under the action of peroxy acid and alkali; and carrying out post-treatment to obtain chlorzoxazone. The problems that polymerization impurities are generated by using 2-amino-4-chlorophenol as a starting material and are difficult to refine and remove, and the purity of the product is influenced are solved. Compared with the prior art, the method has the advantages that the yield and purity of the obtained product are higher, and the method is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis method of chlorzoxazone. Background technique [0002] Chlorzoxazone (Chlorzoxazon, Chlorzoxazon), chemically called 5-chloro-2 (3H)-benzoxazolone, is a powerful oral muscle relaxant, developed by McNeil Pharmaceuticals in the United States, and Listed in the mid-1960s. Chlorzoxazone has been mass-produced in the United States and Japan, and is recorded in the 24th edition of the United States Pharmacopoeia and the 13th edition of the Japanese Pharmacopoeia. This product is one of the 100 commonly used drugs in the United States in recent years, and is listed in the "National Basic Medical Insurance Drug Catalog" and "National Non-Prescription Drug Catalog" in China. This product is a central muscle relaxant, which mainly acts on the spinal cord and the subcortical center of the cerebral cortex, inhibits the polysynaptic nerve reflex arc relat...

AI Technical Summary

Problems solved by technology

[0007] The first method has higher requirements on equipment, and needs to prepare chlorzoxazone with carbon monoxide under high pressure under the condition of noble metal as catalyst. The cost of this method is relatively high, and the process operation is difficult

The second method is prepared by Hofmann rearrangement reaction. Although the reaction conditions are mild, 5-chlorosalicylamide is not easy to obtain. It is limited to laboratory level research and industrial production is difficult.

[0008] The above-mentioned processes all use substituted chlorophenols to prepare chlorzoxazone. In the preparation process using urea as the cyclization reagent in Method 3, the cyclization is initially carried out in a strong acid environment, but a large amount of ammonia will be produced due to the degradation of urea in the later stage of the reaction. Gas, so that the whole reaction system is neutral to weakly alkaline, the nucleophilicity of the amino group under this system is significantly enhanced compared with the acidic environment, and the reaction is carried out at high temperature, so a small amount of polymer (crude product and Crude product, crude product and starting material, starting material and crude product, starting material and starting material), difficult to refine and remove, affecting the purity of the product

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