Atorvastatin calcium side chain intermediate preparation method

Abstract

The present invention provides an atorvastatin calcium side chain intermediate preparation method comprising the following steps: (1) a compound II is added into 2,2-dimethoxypropane liquid, the molar ratio of compound II to 2,2-dimethoxypropane is 1: 2.2 to 13.2; (2) an acidic resin catalyst with the mass accounting for 2.6 to 9.5% of the mass of the compound II is added, and at 10-30DEG C, the mixture is stirred for reaction for 4-6 hours; and (3) the reaction system is filtered, filtrate is concentrated to obtain an oil matter, and the oil matter is recrystallized to obtain a solid atorvastatin calcium side chain intermediate I. By the method, the solid atorvastatin calcium side chain intermediate I with the purity of more than 99% is obtained, and the yield is greater than 95%. The reaction conditions are mild, decolorization treatment is not required, production cost is low, the reaction is stable and easy to control, safety is high, operation is easy, the catalyst and the reactant 2,2-dimethoxypropane are recyclable, waste liquids and waste residues are not produced, and the method is green and environmentally-friendly.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a preparation method of an atorvastatin calcium side chain intermediate. Background technique [0002] With the improvement of people's living standards and changes in lifestyle, the incidence of hyperlipidemia is increasing year by year. In recent years, active treatment of hyperlipidemia has become one of the important means to prevent cardiovascular and cerebrovascular diseases and reduce mortality. Statins are currently the main lipid-lowering drugs, and their lipid-lowering effects are mainly manifested in the inhibition of the rate-limiting enzyme 3-hydroxy-3-methyl-CoA reductase in the process of cholesterol biosynthesis, and the reduction of free cholesterol in cells , Accelerate the clearance of very low-density lipoprotein particles and low-density lipoprotein in the circulation, and finally reduce the level of total cholesterol and low-dens...

AI Technical Summary

Problems solved by technology

The side chain intermediate Ⅰ of atorvastatin calcium is the key side chain intermediate of synthesizing atorvastatin calcium. The synthetic method mainly uses acetone as a solvent, and passes through compound Ⅱ (molecular formula) under the action of a catalyst. ) react with 2,2-dimethoxypropane to generate atorvastatin calcium side chain intermediate Ⅰ (molecular formula ), in the course of operation, p-toluenesulfonic acid is generally selected as the catalyst, after the reaction needs to be extracted with an organic solvent, the organic phase is washed with alkali, and the operation steps such as drying, the color of the product obtained is darker, and it needs to be decolorized with activated carbon to obtain a qualified product. The steps are cumbersome, waste water and residue are generated, and the cost is high

Atorvastatin calcium side chain intermediate I as the key side chain intermediate of atorvastatin calcium preparation method has no patent report