Method for preparing safe and effective antibechic dimimorfan phosphate

Abstract

The invention relates to a method for preparing a safe and effective antibechic dimimorfan phosphate. The method comprises steps of reacting dextrorphane with trifluoro-methylsulfonyl chloride in triethylamine so as to generate dextrorphane trifluoro-methyl sulfone chloride ester; reacting the dextrorphane trifluoro-methyl sulfone chloride ester with tetramethyltin in methylbenzene so as to generate (9s, 13s, 14s)-3, 17-dimethyl morphinan (or adding the dextrorphane trifluoro-methyl sulfone chloride ester into mixed solvent of THF and N-methyl-2-pyrrolidone, adding catalyst ferric acetylacetonate and methyl magnesium bromide, stirring and heating reflux for 12 hours, so as to prepare (9s, 13s, 14s)-3, 17-dimethyl morphinan), furthermore, reacting with phosphoric acid so as to salify to prepare target product (9s, 13s, 14s)-3, 17-dimethyl morphine phosphate-dimimorfan phosphate. The method takes commercially available dextrorphane as the raw material, and prepares the target product through three steps of esterification, methylation and salification. The method has advantages of easily obtained raw materials, few synthesis steps, simple technology, low cost, high yield, high purity of the product and strong economic practicability, and is applicable to industrial production.

Description

technical field [0001] The invention relates to a method for preparing a non-addictive central antitussive drug dimethylorphin phosphate, which inhibits the medulla medulla cough center, and belongs to the technical field of drug synthesis. Background technique [0002] A cough is a sudden forceful breathing movement caused by stimulation of the respiratory center in the medulla. Antitussives are divided into central antitussives and peripheral antitussives according to their different sites of action. Centrally acting antitussives act by inhibiting the medullary cough center and are indicated for dry, nonphlegmous coughs. Peripheral antitussives exert antitussive effect by inhibiting the receptors, afferent nerves, efferent nerves or effectors in the cough reflex arc outside the cough center. [0003] Dimethylorphin phosphate was developed by Fujisawa Pharmaceutical Co., Ltd., Japan, and later merged by Yamanouchi Pharmaceuticals. The marketed product name is Astomin. Dim...

AI Technical Summary

Problems solved by technology

[0010] Although this process does not require splitting, the reaction time is long, the reaction conditions are harsh (requires high temperature and high pressure), the product yield is low, and the production cost is high