Preparation method of intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone of Prasugrel

A technology of hydroxyethanone and trans-2-o-, which is applied in the field of preparation of prasugrel intermediate 1-cyclopropyl-2--2-hydroxyethanone, can solve the problems of high cost and low yield, Achieve the effect of reducing manufacturing steps, promoting development, and improving atom economy

Active Publication Date: 2012-10-10
山东立新制药有限公司
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  • Abstract
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Problems solved by technology

[0016] In summary, in the current method for preparing intermediate A, either expensive raw materials are use

Method used

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  • Preparation method of intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone of Prasugrel
  • Preparation method of intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone of Prasugrel
  • Preparation method of intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone of Prasugrel

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Example Embodiment

[0031] The technical solution of the present invention will be described in further non-limiting detail below in conjunction with preferred embodiments.

[0032] Prasugrel intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyethanone (abbreviated as intermediate A) is one of the important intermediates for the synthesis of prasugrel, and its structural formula is as follows:

[0033]

[0034] According to the mechanism of the improved ketone-alcohol coupling reaction (Acyloin Reaction), the present invention provides a new method for preparing the above-mentioned prasugrel intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyethyl The method for ketone, its synthetic route is as follows:

[0035]

[0036] This preparation method mainly comprises the steps:

[0037] (a) Carry out acylation reaction with industrial raw material bicyclo[2.2.1]heptane-trans-2,3-diol (I) and cyclopropylformyl chloride to obtain the intermediate trans-2-hydroxyl-3-O- (1-cyclopropyl)formy...

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Abstract

The invention discloses a preparation method of an intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone (A) of Prasugrel. According to the preparation method, industrial original bicyclo [2.2.1] heptane-trans-2, 3-glycol (I) has an acylation reaction with cyclopropanecarboxylic acid chloride and fluorobenzoyl chloride in sequence to obtain a intermediate which is trans-2-hydroxy-3-O-(1-cyclopropyl) formyloxy bicycleo [2.2.1] heptane and an intermediate which is trans-2-O-(1-cyclopropyl) formyloxy-3-O-(2-fluorophenyl) bicycle [2.2.1] heptane (II and III); the intermediate (III) has an acyloin reaction under the action of a reducing agent so as to produce 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyacetophenone (A) which is an intermediate of Prasugrel. The preparation method disclosed by the invention is simple and convenient, and can improve the atom economy, the process simplicity and the environmental friendliness.

Description

technical field [0001] The invention relates to the technical field of organic synthesis route design and preparation of raw materials and intermediates, in particular to the preparation of a prasugrel intermediate 1-cyclopropyl-2-(2-fluorophenyl)-2-hydroxyethanone method. Background technique [0002] Prasugrel is a thienopyridine oral anticoagulant jointly developed by Japan's Daiichi Sankyo Pharmaceutical Co., Ltd. and Eli Lilly and Company of the United States. On February 25, 2009, prasugrel hydrochloride tablets were first approved by EMEA for marketing in Europe. In July of the same year, it was approved by the US FDA. In 2010, SFDA approved the import of prasugrel hydrochloride tablets. [0003] The medicinal active ingredient of prasugrel hydrochloride is prasugrel, and its chemical name is 2-[2-(acetyloxy)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)- Base]-1-cyclopropyl-2-(2-fluorophenyl)ethanone, its structural formula is as follows: [0004] [0005] The prepara...

Claims

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Application Information

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IPC IPC(8): C07C49/573C07C45/54
Inventor 许学农王喆张青舒亮苏健包志坚
Owner 山东立新制药有限公司
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