A kind of preparation method of pitavastatin calcium intermediate

Abstract

The invention discloses a preparation method of pitavastatin calcium intermediate, 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 to obtain substance B through the action of an oxidizing agent; finally react with 2-cyclopropyl-4-(4-fluorophenyl ) quinoline-3-formaldehyde is reacted under the catalysis of sodium hydride to obtain pitavastatin calcium intermediate. The raw material of the present invention is cheap and easy to obtain, good atom economy, green and environmental protection, mild and controllable reaction conditions, simple operation, simple purification treatment, suitable for industrial production, good stereoselectivity, high yield, and the prepared pitavastatin calcium intermediate Good purity.

Description

technical field [0001] The invention relates to the technical field of chemical substance preparation, in particular to a preparation method of pitavastatin calcium intermediate. Background technique [0002] The disclosed function of pitavastatin calcium is a blood lipid-lowering drug (HMG-CoA reductase inhibitor), which is the first fully synthetic HMG-CoA reductase inhibitor jointly developed by Nissan Chemical and Kowa Co., Ltd. Belonging to statin drugs, it mainly reduces the ability of the liver to produce cholesterol by inhibiting a liver enzyme called HMG-CoA reductase, so as to improve the elevated blood cholesterol level, and is mainly used for the treatment of hypercholesterolemia and For patients with familial hypercholesterolemia, its lipid-lowering effect is very good, and it is the most powerful lipid-lowering drug so far. Therefore, it is of great significance to study the synthetic route of pitavastatin calcium. [0003] 6-[[(1E)-2-cyclopropyl-4-(4-fluorop...

AI Technical Summary

Problems solved by technology

[0009] From the above review, it can be seen that the main difficulty in the synthesis of pitavastatin calcium is the reaction effect with the stereoselectivity of the docking product.

The above-mentioned route is either because of the expensive raw materials and poor atom economy, or because the reaction conditions are relatively harsh and requires column chromatography, or because the post-processing is difficult to obtain pitavastatin calcium with high purity, so that there is a bottleneck in the industrial production of the above-mentioned route. , so the development of raw materials is cheap and easy to get, the reaction conditions are mild, and the synthetic route of pitavastatin calcium intermediate with good atom economy has broad prospects

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