A kind of preparation method of high-purity esomeprazole sodium

Abstract

The invention discloses a preparation method for high-purity esomeprazole sodium. The preparation method comprises the steps of: including and splitting esomeprazole sodium and D-(-)-diethyl tartrate, titanium iso-propylate, triethylamine and L-(+)-mandelic acid in the presence of a proper amount of water, and separating to obtain an inclusion complex; dissolving the inclusion complex with ethyl acetate, washing inclusion complex with sodium carbonate water solution, carrying out ammonia hydroxide eluting on an ethyl acetate layer, slowly regulating the pH value to 6-7 with glacial acetic acid, then extracting with dichloromethane, and concentrating to obtain crude esomeprazole free alkali product; carrying out silica gel adsorption and elution on the crude product to obtain a pure esomeprazole free alkali product; and enabling the pure product and the methanol-ethanol-acetonitrile solution of sodium hydroxide to form salt, and then crystallizing with isopropyl ether to obtain the high-purity esomeprazole sodium. According to the preparation method, the difficulties that when inclusion and splitting are carried out, the titanium complex suspension body are difficult to split and the ammonia complex of titanium is difficult to remove can be solved, the industrialization production can be realized, the industrialized production cost is low, the product purity is high, the yield is high, and no harmful gas is generated.

Description

technical field

[0001] The invention belongs to the technical field of chemical pharmacy and relates to a preparation method of high-purity esomeprazole sodium. Background technique

[0002] Esomeprazole sodium (Esomeprazolesodium, C 17 h 18 N 3 NaO 3 S), the S-optical isomer of omeprazole, is the world's first isomer proton pump inhibitor (PPI), which reduces gastric acid secretion by specifically inhibiting the proton pump of gastric parietal cells. A large number of clinical experiments and drug studies have confirmed that it can maintain gastric pH>4 for a longer time, have higher acid suppression efficiency, and have better curative effect than the previous two generations of PPI, with little individual difference. As a new generation of PPI, it has been widely used in clinical treatment of many acid-related diseases.

[0003] Inclusion resolution is a chiral drug resolution method developed in this year. During its production, it is easy to produce titanium com...