Synthesizing process of 4-methoxy-alpha-[(3-methoxyphenyl)sulfo]-acetophenone

Abstract

The invention relates to a synthesizing process of 4-methoxy-alpha-[(3-methoxyphenyl)sulfo]-acetophenone, belonging to the synthesizing technique of medical intermediates. The synthesizing process comprises the following steps of dissolving alpha-bromo-4-methoxyphenyl-acetophenone in ethanol, and obtaining the 4-methoxy-alpha-[(3-methoxyphenyl)sulfo]-acetophenone by adding the mixed liquid of potassium hydroxide solution and 3-methoxy-thiophenol ethanol solution. The invention has the advantages of convenient operation, low cost, high purity and high yield rate.

Description

technical field The invention relates to a synthesis process of α-[(3-methoxyphenyl)thio]-4-methoxyacetophenone, which belongs to the synthesis technology of pharmaceutical intermediates. Background technique Raloxifene (English name: raloxifene) is an osteoporosis treatment drug developed by Eli Lilly. In the synthesis process of the drug, the common synthetic route takes 3-methoxythiophenol and α-bromo-4-methoxyacetophenone as starting materials, and undergoes condensation, cyclization, acylation and dehydration. Methylation and other reactions obtained. Wherein α-[(3-methoxyphenyl)thio]-4-methoxyethanone is the intermediate product of the first-step condensation reaction in the preparation process of raloxifene (as shown in the figure below): In the preparation of α-[(3-methoxyphenyl)thio]-4-methoxyacetophenone intermediates, there are not many reported preparation conditions. Wherein U.S. Patent (US 6472531, US 5523416) reported method is: first dissolve 3-methoxy t...

AI Technical Summary

Problems solved by technology

The disadvantages of this process are: (1) The batch feeding is not uniform, the feeding must be cooled in ice salt water, and the added solids are difficult to dissolve in the solution, resulting in incomplete reaction and more impurities

(2) Based on the incomplete reaction, the post-treatment of the reaction product is complicated, and two new solvents are needed for extraction and refining, resulting in a decrease in yield, an increase in cost, and an increase in three wastes

However, this process still involves solvent distillation, ethyl acetate extraction and methanol refining, etc., and the yield cannot be improved.

And the mixed organic solvent of ethanol and ethyl acetate is used, and the manufacturing cost is still too high

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