Atorvastatin calcium compound and new method thereof

Abstract

The invention relates to an atorvastatin calcium compound and a new method thereof. The method comprises the steps of: taking 2-(2-(4-fluorophenyl)-2-oxo-1-phenyl ethyl)-4-methyl-3-oxo-N-phenyl valeramide as starting material, leading the starting material to have aldolization reaction with 3-amino-propionaldehyde glycol to obtain intermediate (II); then, carrying out acidification and obtaining intermediate (III); selecting and using chiral catalyst 2-deoxidized-D-ribose 5-aldolase phosphate for catalyzing the intermediate (III) and acetaldehyde, and obtaining intermediate (V); and finally, under the action of sodium hydroxide, using the intermediate (V) and calcium acetate to generate the atorvastatin calcium compound. The new method of the atorvastatin calcium compound overcomes the defects of the prior art, has simple reaction steps, high purity of obtained product and low production cost, and can be used for industrialized production.

Description

technical field [0001] The invention relates to an atorvastatin calcium compound and a new method thereof, belonging to the technical field of medicine. Background technique [0002] Atorvastatin calcium, chemical name [R-(R,R)]-2-(4-fluorophenyl)-b,d-dihydroxy-5-(1-methylethyl)-3-benzene Base-4-[(anilino)carbonyl]-1 hydrogen-pyrrole-1-heptanoic acid calcium salt trihydrate, the molecular formula is (C 33 h 34 FN 2 o 5 ) 2 Ca·3H 2 O, the molecular weight is 1209.42, and the structural formula is: [0003] [0004] Atorvastatin Calcium was first marketed by Warner Corporation of the United States. It belongs to statin drugs and is currently the most effective drug that can be used to reduce the concentration of low-density lipoprotein ions in the blood stream of patients at risk of cardiovascular diseases. Atorvastatin calcium reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver, and enhances LDL up...

AI Technical Summary

Problems solved by technology

There are certain shortcomings in this approach. The preparation of atorvastatin calcium from lactone is equivalent to increasing the reaction steps and increasing the production cost.

[0007] In the patent document WO01 / 72706, tert-butyl ester is used to protect the side chain acid, hydrolyzed to obtain sodium salt, then acidified to generate atorvastatin acid, and then ammonium salt is precipitated, atorvastatin ammonium is added to isopropyl ether / isopropanol Calcium acetate to obtain atorvastatin calcium, the process is more complicated

[0008] In Chinese patent CN1561341, calcium hydroxide is used to directly hydrolyze atorvastatin ester to obtain calcium salt. The shortcoming of this reaction is that there is no purification step in the reaction mixture, and product precipitation is directly obtained during hydrolysis, and the product purity is not high. It is easy to react with carbon dioxide in the air to form calcium carbonate and become turbid, and the generated calcium carbonate will be difficult to separate from the final product when filtered

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