Pitavastatin calcium intermediate preparation method

Abstract

The invention discloses a pitavastatin calcium intermediate preparation method. The method includes steps: subjecting (4R-Cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethylester and paratoluensulfonyl chloride to sulfonylation reaction under the catalyst action to obtain (4R-Cis)-6-para-toluenesulfonyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester; subjecting to reaction with trimercapto-s-triazine under the action of a basic catalyst to obtain a substance A; subjecting to oxidization under the action of an oxidant to obtain a substance B; finally subjecting to reaction with 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-formaldehyde under the catalytic action of sodium hydride to obtain a pitavastatin calcium intermediate. The pitavastatin calciumintermediate preparation method has advantages of cheapness and easiness in acquisition of raw materials, high atom economy, environmental friendliness, mildness and controllability of reaction conditions, simplicity in operation and purification treatment, suitableness for industrial production, high stereoselectivity and high yield, and the prepared pitavastatin calcium intermediate is high inpurity.

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...

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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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