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Preparation method of 7-hydroxy-1-tetralone

A technology of tetralone and hydroxyl group is applied in the field of preparation of pharmaceutical intermediate 7-hydroxy-1-tetralone, and can solve the problems of extremely high requirements on equipment and operation safety, difficulty in realizing industrialized production, poor selectivity and the like , to achieve the effect of improving environmental friendliness, simplifying operation and meeting quality requirements

Active Publication Date: 2017-07-25
JIANGXI SYNERGY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the method has poor selectivity and low yield
In addition, fluoroantimonic acid is a super acid with strong corrosiveness, which requires extremely high equipment and operation safety, and it is difficult to realize industrial production

Method used

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  • Preparation method of 7-hydroxy-1-tetralone
  • Preparation method of 7-hydroxy-1-tetralone
  • Preparation method of 7-hydroxy-1-tetralone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Preparation of 4-(4-methoxyphenyl)-4-oxobutanoic acid

[0034] Put 250ml of nitromethane and 30g of anisole into a 500ml reaction bottle, add 80g of anhydrous aluminum trichloride at a temperature of 0-15°C, keep stirring for 2 hours, then add 25g of succinic anhydride, and react at a temperature of 10-20°C for 12 hours . The reaction solution was added to a system of 600ml water-100ml 30% hydrochloric acid, the temperature was controlled at 0-25°C, and the mixture was kept stirring for 1 hour. Suction filtration and drying yielded 49.1 g of 4-(4-methoxyphenyl)-4-oxobutanoic acid with a yield of 92% and a purity of 99.5% by HPLC.

Embodiment 2

[0035] Example 2 Preparation of 4-(4-methoxyphenyl)-4-oxobutanoic acid

[0036] In a 500ml reaction bottle, put 250ml of dichloromethane and 50g of anisole, add 120g of aluminum tribromide at a temperature of 0-15°C, stir and keep warm for 2h, add 43g of succinic anhydride, and keep the temperature at -5-20°C for 12h. The reaction solution was added to a system of 600ml water-100ml 30% hydrochloric acid, the temperature was controlled at 0-25°C, and the mixture was kept stirring for 1 hour. After suction filtration, the filter cake was dried under reduced pressure at 60°C to obtain 76.5 g of 4-(4-methoxyphenyl)-4-oxobutanoic acid, with a yield of 86% and a purity of 98.7% by HPLC.

Embodiment 3

[0037] Example 3 Preparation of 7-Hydroxy-1-tetralone

[0038] Put 200ml of toluene, 44g of aluminum trichloride, 10ml of nitromethane into a 500ml reaction bottle, dissolve at 60-70°C, add 4-(4-methoxyphenyl)butyric acid (prepared according to the method described in Example 1) 20g. The temperature was raised to reflux for 10 hours, and the reaction solution was added to 300 ml of ice water. Stand for stratification, discard the water layer, add 100ml of water to the organic layer, adjust the pH to 13 with liquid caustic soda, let stand for stratification, discard the organic layer, adjust the pH of the water layer to 2 with hydrochloric acid, filter, add methanol to the filtrate 20ml and 30ml of water were heated and refluxed to dissolve, cooled to 0°C to crystallize, filtered, and the filter cake was dried to obtain 14.7g of white solid 7-hydroxy-1-tetralone, with a yield of 88%, and a purity of 99.99% by HPLC. See atlas figure 1 .

[0039] 1 H-NMR (CDCl 3 ,400MHz)...

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Abstract

The invention relates to a preparation method of 7-hydroxy-1-tetralone with a structural formula I. 4-(4-methoxyphenyl)butyric acid with a structural formula II is used as a starting material, in the presence of Lewis acid, a one pot process is used for carrying out cyclization and a demethylating reaction, and 7-hydroxy-1-tetralone is obtained. The preparation method has simple operation, phosphorus-containing reagents are not used, and environmental friendliness of the reaction is improved; in addition, yield of 7-hydroxy-1-tetralone is high (higher than 85%), and purity is good (high than 99.9%). Accordingly the method is completely suitable for industrial production, and satisfies requirements on quality of intermediates in medical industry.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and in particular relates to a preparation method of a useful pharmaceutical intermediate 7-hydroxyl-1-tetralone. Background technique [0002] 7-Hydroxy-1-tetralone is a useful intermediate for synthesizing various active fused ring compounds, such as prostaglandins and velpatasvir. Its structural formula is shown in I, and its CAS number is: 22009-38-7. [0003] [0004] The synthetic train of thought of 7-hydroxyl-1-tetralone reported in the prior art can be roughly divided into two kinds: a kind of is that 7-methoxyl-1-tetralone demethylation obtains 7-hydroxyl- 1-tetralone; the other is to substitute the hydroxyl group on the phenyl group of 1-tetralone to obtain 7-hydroxyl-1-tetralone. But both methods have deficiencies. [0005] The reaction scheme of the first method is as follows: [0006] [0007] 7-Methoxy-1-tetrahydronaphthalene was reported in Woo, L.W. Lawrence; Howarth, Ni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C45/00C07C49/733
CPCC07C45/00C07C51/083C07C51/347C07C49/733C07C59/90C07C59/64
Inventor 黄伟平庞泽远冯玉杰徐烘材康禄崔汉峰
Owner JIANGXI SYNERGY PHARMA
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