A kind of preparation method of rosuvastatin sodium

Abstract

The invention discloses a preparation method of rosuvastatin sodium, comprising the following steps: (4R-Cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4- The sulfonylation reaction of tert-butyl acetate and p-toluenesulfonyl chloride under the action of a catalyst gives (4R-Cis)-6-p-toluenesulfonyl-2,2-dimethyl-1,3-dioxane-4 ‑tert-butyl acetate; then react with trimercapto-s-triazine under the action of a basic catalyst to obtain substance A; then oxidize with oxidant to obtain substance B; then react with 4‑(4‑fluorophenyl)‑6‑isopropyl ‑2‑[(N‑Methyl‑N‑methylsulfonyl)amino]pyrimidine‑5‑formaldehyde is reacted under the catalysis of sodium hydride to obtain substance C; finally deprotected by hydrochloric acid, and sodium hydroxide is hydrolyzed into a salt to obtain rosuvastatin sodium.

Description

technical field [0001] The invention relates to the technical field of chemical substance preparation, in particular to a preparation method of rosuvastatin sodium. Background technique [0002] Rosuvastatin Calcium is an anti-hyperlipidemic drug, which is an HMG-CoA reductase inhibitor, successfully developed by British AstraZeneca, and is suitable for the treatment of various lipid abnormalities, including hypercholesterolemia, mixed lipid Massive disorders and simple hypertriglyceridemia. Rosuvastatin calcium is the statin drug with the strongest lipid-lowering effect and the most comprehensive lipid-lowering effect among the blood-lipid-lowering drugs currently on the market. It has better lowering of LDL cholesterol and Improve the effect of high-density lipoprotein, and have better tolerance, lower side effects and unique pharmacokinetic characteristics, rosuvastatin sodium is the precursor of rosuvastatin calcium, therefore, study rosuvastatin The synthetic route of...

AI Technical Summary

Problems solved by technology

[0019] Although the stereoselectivity of docking in this route has been well resolved, the side chains are difficult to obtain, the atom economy of the reaction is poor, and the olefination reaction temperature is -60°C, which requires high equipment, which makes the industrial production of this route difficult.

[0020] From the above review, it can be seen that the current synthesis of rosuvastatin sodium is difficult to obtain because of expensive raw materials, or because the route is complex and the total yield is low, or because the reaction conditions are harsh, it is difficult to realize industrial production, or because of the poor stereoselectivity, the cost of the route is high. , so the development of cheap and easy-to-obtain raw materials, mild reaction conditions, and good atom economy has broad prospects

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