Method for preparing benzbromarone

A technology of benzbromarone and compounds, applied in the field of compound preparation, can solve problems such as easy hydrolysis and unsmooth reaction

Active Publication Date: 2020-08-14
ZHEJIANG HAIZHOU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 1. In the process of acetylation protection, by-products of carboxyl acetylation will inevitably be produced, which will lead to the failure of subsequent reactions to proceed smoothly
[0010] 2. Due to the ester group structure formed by acetylation to protect the hydroxyl group, it is very easy to hydrolyze, so that hydroxyl chlorination occurs in the subsequent acyl chloride reaction, and other by-products are produced

Method used

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  • Method for preparing benzbromarone
  • Method for preparing benzbromarone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Preparation of 3,5-dibromo-4-tetrahydropyranyl ether-benzoic acid (compound Ⅱ)

[0044] Add 200ml of dihydropyran, 10g of 3,5-dibromo-4-hydroxybenzoic acid, and 3g of aluminum phosphate into a 500ml reaction bottle, heat up to reflux, stir for 3 hours, cool down to room temperature, and filter off the solid Aluminum phosphate, 0.01MPa reduced pressure distillation to remove excess dihydropyran, to obtain 12.16 g of oily compound II, yield 95%, no raw material spots on TLC spot plate, TLC developer is ethyl acetate: n-hexane: acetic acid = 4: 1:0.1.

Embodiment 2

[0045] Example 2: Preparation of 3,5-dibromo-4-tetrahydropyranyl ether-benzoyl chloride (compound III)

[0046]Add 12g of the product of Example 1 into a 500ml reaction flask, add 200ml of dichloromethane, 1 drop of dimethylformamide (DMF), 8.17g of N,N-diisopropylethylamine, and stir at 15-20°C After 30 minutes, add 7.5g of thionyl chloride dropwise, and the dropping rate is controlled at an internal temperature not exceeding 25°C. After the dropwise addition is completed, keep stirring at 30-35°C for 5 hours, and filter out N,N-diisopropylethylamine. Hydrochloride, dichloromethane and excess thionyl chloride were evaporated to dryness under reduced pressure at 30°C to obtain an oily substance, which was dissolved by adding 100ml of dichloromethane, then washed and extracted by adding 100ml of saturated sodium chloride solution, and the organic layer was extracted with anhydrous sulfuric acid Magnesium was dehydrated and evaporated to dryness to obtain 12.1 g of oily compound...

Embodiment 3

[0047] Example 3: Preparation of (3,5-dibromo-4-tetrahydropyranyl ether phenyl) (2-ethyl-3-benzofuryl) ketone (compound IV)

[0048] Add 12g of compound III prepared in Example 2 into a 500ml dry reaction flask, add 200ml of dichloromethane, add 5.3g of 2-ethyl-3-benzofuran, cool down to -5°C and stir for 30min, then add 10g of aluminum trichloride, stirred and reacted for 5 hours. At this time, the color of the reaction solution changed from light yellow to dark brown. Slowly add 100ml of ice water to control the internal temperature not to exceed 5°C. The aqueous layer and the organic layer were washed twice with 100ml of saturated sodium chloride solution, then the organic layer was dehydrated by adding anhydrous magnesium sulfate, and evaporated to dryness to obtain 14g of oily compound IV with a yield of 91.5% and a purity of 96% by HPLC.

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Abstract

The invention discloses a method for preparing benzbromarone. According to the method, 3, 5-dibromo-4-hydroxybenzoic acid is used as a raw material, dihydropyran is used as a hydroxyl protection reagent to prepare benzbromarone, and dihydropyran hydroxyl protection and hydroxyl deprotection are realized through explored optimized process conditions so that the purposes of reducing the generation of byproducts in the reaction process, increasing the yield and reducing the cost are achieved.

Description

technical field [0001] The invention relates to the technical field of compound preparation, in particular to a method for preparing benzbromarone. Background technique [0002] Chemical name: (3,5-dibromo-4-hydroxyphenyl)(2-ethyl-3-benzofuryl)ketone [0003] English name: (3,5-dibromo-4-hydroxyphenyl)(2-ethyl-3-benzofuranyl)keton [0004] Structural formula: [0005] Molecular formula: C 17 h 12 Br 2 o 3 [0006] Molecular weight: 424 [0007] Benzbromarone, also known as bromobenzoyl benzofuran, is a powerful uric acid-removing benzofuran derivative, which has a strong uric acid-removing effect. The compound can not only effectively inhibit the reabsorption of uric acid by renal tubules, but also promote the excretion of uric acid, and has dual functions for reducing blood uric acid concentration. [0008] In US20190218243 and CN201310191043.8, a synthesis method of related intermediates or benzbromarone is described, both of which are protected by acetylation w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/80
CPCC07D307/80Y02P20/55
Inventor 赵旭杨甫余
Owner ZHEJIANG HAIZHOU PHARMA CO LTD
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