Preparation method of 2-methyl-1-tetralone

A technology of tetralone and methyl, which is applied in the field of synthesis of tetralone derivatives, can solve the problems of low yield of 2-methyl-1-tetralone, cumbersome post-processing steps, column chromatography, etc. , to achieve the effect of short preparation route, avoiding ultra-low temperature reaction, and simple purification

Active Publication Date: 2021-10-29
BTC PHARMA TECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The application provides a preparation method of 2-methyl-1-tetralone, which aims to solve the problem that in the prior art, the yield of 2-methyl-1-tetralone is low, and the post-treatment steps require cumbersome Problems with Column Chromatography

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  • Preparation method of 2-methyl-1-tetralone
  • Preparation method of 2-methyl-1-tetralone
  • Preparation method of 2-methyl-1-tetralone

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preparation example Construction

[0022] The embodiment of the present application provides a preparation method of 2-methyl-1-tetralone, the preparation method comprising:

[0023] Add the dipolar aprotic solvent and sodium hydride into the reaction flask, add 1-tetralone dropwise at 15-35°C, add dimethyl carbonate dropwise after stirring, and control the internal temperature at 45-55°C ℃.

[0024] Cool down to 0-30°C, add methylating reagent dropwise, and place at 0-15°C for 6-18h reaction. The methylating reagent is methyl trifluoroacetate, methyl p-benzenesulfonate or methyl bromide.

[0025] Add acidic aqueous solution dropwise, add water and stir to separate layers, extract with extractant, combine organic phases, and precipitate to obtain a crude product, which is recrystallized to obtain 1-tetralone-2-methyl-2-carboxylic acid methyl ester .

[0026] Add hydrobromic acid to the 1-tetralone-2-methyl-2-carboxylic acid methyl ester, add water, add toluene, add acetic acid, heat, keep the temperature at 9...

Embodiment 1

[0037] Synthesis of 1-tetralone-2-methyl-2-carboxylic acid methyl ester

[0038]

[0039]In a 1000mL four-neck flask, add 320g tetrahydrofuran, add 19.63g (0.5mol, 2.1e.q.) 60% sodium hydride, and add 35g (0.24mol, 1.0e.q.) 1-tetralone dropwise at 25°C After 1 hour, start to add 26g (0.289mol, 1.2e.q.) of dimethyl carbonate dropwise, control the internal temperature between 45-55°C, and complete the addition.

[0040] Cool down to 15°C, and add 68g (0.53mol, 2.2e.q.) of methyl trifluoroacetate dropwise at 15-20°C, and keep the temperature at 25°C for 10h after the dropwise addition.

[0041] Add dropwise 65 g of saturated ammonium chloride aqueous solution to quench below 20°C. Add 200mL of water to stir and separate the layers, separate the liquid, extract the water phase with 150mL of toluene twice, combine the organic phase, force out the water in the organic phase with 150mL of saturated saline, spin the organic phase, crystallize the crude product with 500mL of petrol...

Embodiment 2

[0046] Synthesis of 1-tetralone-2-methyl-2-carboxylic acid methyl ester

[0047]

[0048] In a 2000mL reaction flask, add 600g tetrahydrofuran, add 45g (1.125mol, 2.05e.q.) 60% sodium hydrogen, drop 80g (0.55mol, 1.0e.q.) 1-tetralone at 25°C, and after 1h, start Add 90 g (1.0 mol, 1.8 e.q.) of dimethyl carbonate dropwise, control the internal temperature between 45-55° C., and complete the addition.

[0049] Cool down to 15°C, add 204.8g (1.1mol, 2.0e.q.) methyl p-toluenesulfonate dropwise between 15-20°C, and keep warm at 25°C overnight after the dropwise addition.

[0050] 130 g of saturated ammonium chloride aqueous solution was added dropwise to quench at 20°C or lower. Add 500mL of water and stir to separate the layers, separate the liquids, extract the aqueous phase twice with 350mL toluene, combine the organic phases, add 70g of triethylenediamine to remove excess methyl p-toluenesulfonate, wash the organic phase with 350mL of saturated brine, spin The organic phas...

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Abstract

The invention relates to the field of synthesis of tetralone derivatives, and provides a preparation method of 2-methyl-1-tetralone. The preparation method comprises the steps of firstly, enabling 1-tetralone to be subjected to hydrogen extraction and methylation by using a one-pot method, replacing a conventional methylation reagent iodomethane with high toxicity with methyl trifluoroacetate, methyl p-benzenesulfonate or methyl bromide, and in the one-pot reaction, generating 1-tetralone-2-methyl-2-methyl formate; and reacting hydrobromic acid with 1-tetralone-2-methyl-2-methyl formate, and collecting a product in a reduced pressure distillation manner in a post-treatment step so as to finally obtain 2-methyl-1-tetralone. The preparation method of 2-methyl-1-tetralone provided by the embodiment of the invention has the advantages of short synthetic route, no need of ultralow-temperature reaction or column chromatography, simple purification and high yield (up to 84.3%).

Description

technical field [0001] The present application relates to the field of synthesis of tetralone derivatives, in particular to a preparation method of 2-methyl-1-tetralone. Background technique [0002] Tetralone compounds are important intermediates of pharmaceutical or chemical raw materials. Using tetralone as raw material, the derivatives of tetralone synthesized by further reaction are widely used in the field of medicine, such as anti-inflammatory, anti-inflammatory Rheumatic, antidiabetic and quinolone drugs. Therefore take tetralone as the demand of the medicine synthesized as intermediate, in order to prepare this class medicine in a large amount, its preparation method appears extremely important. [0003] 2-methyl-1-tetralone is exactly a kind of derivative wherein, yet in actual production, there are harsh reaction conditions, high production cost, Problems such as low yield. The following are two synthetic methods in the prior art: [0004] Prior art 1 (Org. Le...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C45/65C07C49/67
CPCC07C45/65C07C67/00C07C49/67C07C69/757Y02P20/55
Inventor 杨少强鲁斌斌张鹏飞陆毅周广陈国庆
Owner BTC PHARMA TECH CO LTD
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