Chemical synthesis method of (1R, 2S)-2-aryl cyclopropylamine derivative

An arylcyclopropylamine, a technology for chemical synthesis, applied in chemical instruments and methods, purification/separation of amino compounds, organic chemistry, etc., and can solve problems such as low stereoselectivity

Inactive Publication Date: 2013-01-09
NANTONG UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In order to overcome the defect of low stereoselectivity of the existing synthesis method, the present inven

Method used

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  • Chemical synthesis method of (1R, 2S)-2-aryl cyclopropylamine derivative
  • Chemical synthesis method of (1R, 2S)-2-aryl cyclopropylamine derivative
  • Chemical synthesis method of (1R, 2S)-2-aryl cyclopropylamine derivative

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Embodiment 1

[0019] Synthesis of 2-phenyl-cyclopropylcarboxylic acid: Add 10.0 g NaH and 250 ml dimethyl sulfoxide into a three-necked flask under nitrogen protection, and add N-methoxy-N methyl-3-phenylpropene in batches amide 27.4 g, stirred and dissolved for 30 min, then added dropwise 42.0 g trimethylsulfoxide iodide, and reacted at room temperature. After adding water to quench and extract with methyl tert-butyl ether, the organic phase was washed with water three times, dried and concentrated to obtain 25.0 g of light yellow liquid with a yield of 85.0%. Transfer the yellow product to a single-necked bottle, add 200 ml of methanol and 100 ml of water, stir to dissolve, then add 10.0 g of sodium hydroxide, and stir to react overnight. After the reaction was completed, water was added to adjust the pH to 3-4, extracted with dichloromethane, and concentrated to obtain 17.8 g of white 2-phenyl-cyclopropyl formic acid solid with a yield of 90.1%.

[0020] Synthesis of N-Boc-2-phenylcyclo...

Embodiment 2

[0024] Synthesis of 2-(4'-methoxyphenyl)-cyclopropanecarboxylic acid: Add 10.0 g NaH and 300 ml dimethyl sulfoxide into a three-necked flask under nitrogen protection, and add N-methoxy-N 31.7 g of methyl-3-(4'-methoxyphenyl)acrylamide was stirred and dissolved for 30 min, then 42.0 g of trimethylsulfoxide iodide was added dropwise, and reacted at room temperature. It was quenched by adding water, extracted with methyl tert-butyl ether, washed with water three times, dried and concentrated to obtain 30.0 g of yellow liquid with a yield of 89.0%. Transfer the yellow product to a single-necked bottle, add 250 ml of methanol and 125 ml of water, stir to dissolve, then add 10.0 g of sodium hydroxide, and stir to react overnight. After the reaction was completed, water was added to adjust the pH to 3-4, extracted with dichloromethane, and concentrated to obtain 22.3 g of light yellow 2-(4'-methoxyphenyl)cyclopropanecarboxylic acid solid, with a yield of 91.0%.

[0025] Synthesis o...

Embodiment 3

[0029]Synthesis of 2-(4'-bromophenyl)-cyclopropanecarboxylic acid: Add 10.0 g NaH and 350 ml dimethyl sulfoxide into a three-necked flask under nitrogen protection, and add N-methoxy-N methyl - 38.7 g of 3-(4'-bromophenyl) acrylamide, stirred and dissolved for 30 min, then added dropwise 42.0 g of trimethylsulfoxide iodide, and reacted at room temperature. It was quenched by adding water, extracted with methyl tert-butyl ether, washed three times with water, dried and concentrated to obtain 32.3 g of yellow liquid with a yield of 79.3%. Transfer the yellow product to a single-necked bottle, add 300 ml of methanol and 150 ml of water, stir to dissolve, then add 10.0 g of sodium hydroxide, and stir to react overnight. After the reaction was completed, adjust the pH to 3-4, extract with dichloromethane, and concentrate to obtain 24.3 g of light yellow 2-(4'-bromophenyl)cyclopropyl formic acid solid, with a yield of 88.6%.

[0030] Synthesis of N-Boc-2-(4'-bromophenyl)cyclopropyl...

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Abstract

The invention relates to a chemical synthesis method of a (1R, 2S)-2-aryl cyclopropylamine derivative. 3-aryl crylic acid serves as a raw material, the raw material and N,O-dimethyl hydroxy amine hydrochloride are subjected reaction to prepare a corresponding amide intermediate, cyclization reaction is conducted, 2- aryl cyclopropylamine is obtained; and finally D-mandelic acid serves as a resolving agent to obtain the (1R, 2S)-2-aryl cyclopropylamine derivative. The method has the advantages of being high in yield and high in e.e. value.

Description

technical field [0001] The invention relates to a chemical synthesis method of (1R,2S)-2-arylcyclopropylamine derivatives. Background technique [0002] (1R,2S)-2-Arylcyclopropylamine derivatives are an important class of chiral pharmaceutical intermediates. Many literatures describe their modification in new anticancer drug molecules. Therefore, the synthesis research of this kind of compounds has important practical significance. [0003] Although (1R,2S)-2-arylcyclopropylamine derivatives have important functions in drug molecules, there are few reports on their synthesis. It has been reported in the literature that (1R,2S)-phenylcyclopropylamine was synthesized by the following route using styrene as a raw material. In general, although this route directly generates a chiral center, its stereoselectivity is not high. [0004] Contents of the invention [0005] In order to overcome the defect of low stereoselectivity of the existing synthesis method, the present i...

Claims

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Application Information

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IPC IPC(8): C07C211/40C07C209/88C07C213/10C07C217/74
Inventor 朱金丽孙同明朱国华王树清喻红梅高鹏飞项蕊张素梅
Owner NANTONG UNIVERSITY
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