Preparation method of esomeprazole potassium

Abstract

The invention discloses a preparation method of esomeprazole potassium. The preparation method comprises the following steps: (1) putting methylbenzene into a dry reaction kettle, and introducing nitrogen into the methylbenzene until the end of centrifugation; (2) putting omeprazole sulfide, rising the temperature to 30 to 32 DG C, and putting 26 KG of D-(-)diethyl tartrate; (3) rising the temperature to 44 to 46 DEG C, and putting isopropyl titanate (IV) after stirring for 30 minutes; (4) cooling to 31 to 35 DEG C, and putting diisopropylethylamine; (5) keeping the temperature be 31 to 33 DEG C, and dropwise adding cumyl hydroperoxide within 30 minutes to 2 hours; (6) keeping the temperature be 31 to 33 DEG C for 15 minutes for reacting; checking the content of sulfide through QC (Quality Control), and monitoring whether the reaction ends or not; (7) after the end of the reaction, stirring a methanol solution of potassium hydroxide; (8) cooling to 25 to 30 DEG C and keeping for 1 hour; (9) centrifuging, thus obtaining a coarse product, and refining further.

Description

technical field

[0001] The invention relates to a preparation method of esomeprazole potassium, which belongs to the field of pharmacy. Background technique

[0002] Esomeprazole magnesium is also known as levo-omeprazole, esomeprazole, chemical name (S)-(-)-5-methoxy-2-{[(4-methoxy-3,5 -Dimethyl-2-pyridyl)methyl]sulfinyl}-1H-benzimidazole magnesium salt, which is the magnesium salt of (S)-(-)-type single enantiomer of the marketed drug omeprazole Salt preparation, developed by Astra Zeneca Company in Sweden, was launched in my country in 2004; it is a new type of proton pump inhibitor, which can inhibit the activity of H+ / K+-ATPase, and is mainly used clinically to treat gastric ulcer caused by excessive gastric acid secretion. Duodenal ulcer and reflux esophagitis and other digestive system diseases.

[0003] The preparation method of the esomeprazole magnesium intermediate esomeprazole potassium published by the patent US6369085B1 (the same family patent WO9854171A) is as ...