Process for preparing key intermediate 2-ethyl-3-p-hydroxybenzoyl-benzofuran of benzbromarone

Abstract

The invention provides a process for preparing a key intermediate 2-ethyl-3-p-hydroxybenzoyl-benzofuran of benzbromarone. The process comprises the following steps of: (1) by taking 2-ethyl-3-p-methoxybenzoyl-benzofuran as a raw material and alkylbenzene as a reaction solvent, reacting the raw material with the reaction solvent in the presence of an acidic catalyst by a certain quantity; (2) after cooling by using ice water, adding a bit of diluted hydrochloric acid and separating out the water layer, performing decompression distillation on the organic layer so as to recover the solvent, and then concentrating the organic layer until the organic layer is dry; (3) adding a diluted basic liquid to the organic layer concentrated liquid obtained in the step (2), separating out the water layer, adding diluted hydrochloric acid to the water layer for adjusting the pH to the range from 1 to 4, and then adding haloalkane for extraction, and slowly distilling the extract until the extract becomes dry, thereby obtaining solid; and (4) performing recrystallization separation on the solid obtained in the step (3) by using petroleum ether, thus obtaining the 2-ethyl-3-p-hydroxybenzoyl-benzofuran of benzbromarone. The yield is over 90% and the liquid phase content is greater than or equal to 98%. The process is easy to control, greatly reduced in cost, and convenient for realizing industrial mass production.

Description

Technical field [0001] The invention relates to a preparation method of pharmaceutical intermediates, in particular to a preparation process of 2-ethyl-3-p-hydroxybenzoyl-benzofuran, a key intermediate of benzbromarone medicine. Background technique [0002] Benzbromarone (Benzbromarone) is a uric acid excretion accelerator developed by the French company Labaz. It was launched in Germany in 1971 and is clinically used to accelerate the excretion of uric acid and the treatment of gout. 2-Ethyl-3-p-hydroxybenzoyl-benzofuran is a key intermediate in the synthesis of benzbromarone. The synthetic methods of 2-ethyl-3-p-hydroxybenzoyl-benzofuran that have been published in domestic and foreign literature are all based on 2-ethyl-3-p-methoxybenzoyl-benzofuran as raw material Pyridine hydrochloride is a catalyst for the reaction at 210-220°C. The catalyst pyridine hydrochloride used in the process is easy to absorb moisture, is difficult to prepare and store, and is difficult to purch...

AI Technical Summary

Problems solved by technology

The catalyst pyridine hydrochloride used in this process is very easy to absorb moisture, it is not easy to prepare and store, and it is difficult to purchase

Due to the quality instability of pyridine hydrochloride, the yield of this step fluctuates greatly (63%-85%)

High temperature reaction at 210-220°C is not conducive to industrialized mass production

The reaction above this temperature requires a special heating method, which not only increases the production cost, but also brings certain hidden dangers to the safe production of the workshop if the temperature is too high

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