Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation

A pitavastatin calcium, asymmetric technology, applied in the field of cholesterol-lowering drugs in the field of medicinal chemistry technology, can solve problems such as the source of chiral side chains, and achieve the effect of solving expensive

Active Publication Date: 2009-03-18
JIANGSU WANBANG BIOPHARMLS +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The purpose of the present invention is to address the deficiencies in the prior art, to provide a method for preparing pitavastatin calcium bulk drug by asymmetric hydrogenation, which mainly solves the problem of the chiral side chain source of pitavastatin calcium bulk drug in the existing preparation

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  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation
  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation
  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation

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Embodiment Construction

[0030] The embodiments of the present invention are described in detail below: the present embodiment is implemented under the premise of the technical solution of the present invention, and detailed implementation and specific operation process are provided, but the protection scope of the present invention is not limited to the following implementation example.

[0031] 1. Preparation of (S)-4-benzyloxy-3-hydroxybutyric acid ethyl ester and chiral catalyst (using Sunphos

[0032] For example, others can be prepared in a similar way). Reaction formula:

[0033]

[0034] Steps

[0035] Schlenk reaction tube, pumped and baked three times, added [RuCl 2 (p-Cymene)] 2 (21.6mg, 35.3μmol, 1eq), Sunphos (56.1mg, 77.0μmol, 2.2eq), replace nitrogen three times, add EtOH / CH 2 Cl 2 (9mL / 3mL), heated to 40°C for 3.5h, and dried to obtain an orange powdery solid catalyst.

[0036]

[0037] In a 150mL small beaker, add I (50.0g, 211.6mmol, 1eq), EtOH (80mL), chiral catalyst (S...

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Abstract

The invention relates to a method for preparing a pitavastatin calcium raw material by asymmetric hydrogenation in the technical field of medicinal chemistry. The method comprises the following steps: performing catalytic hydrogenation on 4-benzyloxy-ethyl-acetoacetate I by using a chiral catalyst to prepare (S)-4-benzyloxy-3-hydroxy-ethyl-butyrate, and then obtaining the pitavastatin calcium through a series of reactions such as Claisen condensation, reduction, hydroxyl protection, removal of benzyl, oxidation and the like. In the invention, the highly-efficient chirality added value is realized by the use of catalytic amount of the chiral catalyst (wherein the ratio of substrate to the catalyst can reach 3, 000 to 1), and by performing the asymmetric hydrogenation and the reduction on non-chiral ketones to generate chiral alcohols compounds directly (wherein the enantioselectivity can be up to 94.3 percent).

Description

technical field [0001] The invention relates to a method for lowering cholesterol drugs in the technical field of medicinal chemistry, in particular to a method for preparing pitavastatin calcium crude drug by asymmetric hydrogenation. Background technique [0002] Pitavastatin calcium is Japanese Patent Application Publication No. 1-279866, EP304063, disclosed in U.S. Patent No. 5011930 as a blood lipid-lowering drug (HMG-CoA reductase inhibitor), and pitavastatin calcium is developed by Japan Nissan Chemical Industry Co., Ltd. And by Nissan Chemical Industry Co., Ltd., Xinghe Co., Ltd. and Sankyo Co., Ltd., it was approved to be listed in Japan in July 2003 for the treatment of hypercholesterolemia. The trade name "LIVALO R ", the formulation specifications are 1mg and 2mg film-coated tablets. [0003] Pitavastatin calcium inhibits the synthesis of cholesterol in the liver by inhibiting the rate-limiting enzyme of cholesterol synthesis, HMG-CoA reductase. Pitavastatin ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/14C07B53/00A61P3/06
Inventor 张兆国范为正孟庆华
Owner JIANGSU WANBANG BIOPHARMLS
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