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Preparation method and application of aromatic cyclopropyl butanone compound

A cyclopropyl ethyl ketone and compound technology, which is applied in the preparation of carbon-based compounds, the preparation of organic compounds, chemical instruments and methods, etc., can solve the problems of complex post-processing, easy to generate danger, etc., and achieve easy processing and easy reaction. The effect of progress and complete reaction

Active Publication Date: 2011-11-16
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This reaction requires a large amount of thionyl chloride as a solvent. We know that thionyl chloride is very irritating and toxic, and the post-treatment is more complicated. For industrialization, a large amount of alkali is required for neutralization, accompanied by a large amount of Sulfur-containing gas is produced and the post-treatment process is also extremely dangerous

Method used

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  • Preparation method and application of aromatic cyclopropyl butanone compound
  • Preparation method and application of aromatic cyclopropyl butanone compound
  • Preparation method and application of aromatic cyclopropyl butanone compound

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Example 1: Preparation of 1-cyclopropyl-2-(2-fluorophenyl)ethanone

[0035] Weigh magnesium (2.88g, 0.12mol), put it into a three-necked reaction flask, under the protection of nitrogen, add 120mL of tetrahydrofuran, activate the magnesium with 0.1mL of 1,2-dibromoethane at 25°C, after the activation is completed, slowly add 1 -(Bromomethyl)-2-fluorobenzene (18.9g, 0.10mol), the internal temperature was controlled at 20-25°C. After the dropwise addition, continue to react at this temperature for about 2 hours, and monitor the reaction by GC until the end of the reaction. At 0° C., a solution of N-methoxy-N-methylcyclopropylcarboxamide (12.9 g, 0.10 mol) dissolved in 200 ml of tetrahydrofuran was added dropwise. After the addition was complete, the reaction was tracked by TLC until the reaction was completed. Saturated ammonium chloride was added, liquid separation, extraction, solvent was evaporated, and the obtained organic layer liquid was distilled under reduced pre...

Embodiment 2

[0037] Example 2: Preparation of 1-cyclopropyl-2-(2-fluorophenyl)ethanone

[0038]Weigh magnesium powder (2.88g, 0.12mol), put it into a three-necked reaction flask, under nitrogen protection, add 120mL of tetrahydrofuran, activate magnesium with 0.1mL 1,2-dibromoethane at 25°C, after the activation is completed, slowly add 1-(Chloromethyl)-2-fluorobenzene (14.46g, 0.10mol), the internal temperature was controlled at 20-25°C. After the dropwise addition, continue to react at this temperature for about 2 hours, and monitor the reaction by GC until the end of the reaction. At 0° C., a solution of N-methoxy-N-methylcyclopropylcarboxamide (12.9 g, 0.10 mol) dissolved in 200 ml of tetrahydrofuran was added dropwise. After the dropwise addition, the reaction was tracked by TLC until the reaction was completed. Saturated ammonium chloride was added, liquid separation, extraction, solvent was evaporated, and the obtained organic layer liquid was distilled under reduced pressure to ob...

Embodiment 3

[0039] Embodiment 3: the preparation of 2-(3-chlorophenyl)-1-cyclopropyl ethyl ketone

[0040] Operate in the same way as in Example 1, weigh 1-chloro-3-(chloromethyl)benzene (16.1g, 0.10mol), and add N-ethoxyl dissolved in 200ml tetrahydrofuran dropwise at 0°C -N-Isopropylcyclopropanecarboxamide (17.1g, 0.10mol) solution to obtain 16.6g of 2-(3-chlorophenyl)-1-cyclopropylethanone with a yield of 85.3%.

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Abstract

The invention relates to the chemical technical field of carbocyclic rings, in particular to a preparation method and application of an aromatic cyclopropyl butanone compound. The preparation method comprises the following steps of: making a compound shown as a formula (a) react with a magnesium elementary substance to obtain a Grignard reagent; undergoing a Grignard reaction on a compound shown as a formula (b) to obtain an aromatic cyclopropyl butanone compound, i.e., a compound shown as a formula (c), wherein the aromatic cyclopropyl butanone compound can be used for preparing a tetrahydrothienopyridine derivative; and when R1 is a two-potential fluorine atom, the compound shown as the formula (c) is an important intermediate for preparing Prasugrel. The structural formula of the related compound is shown in the specifications, wherein R1 refers to F, Cl, alkyl with 1-4 carbon atoms or alkoxy with 1-4 carbon atoms; R2 and R3 refer to alkyls; and X refers to Cl or Br.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to the technical field of carbocyclic chemistry. Background technique [0002] Aromatic cyclopropyl ethyl ketones are important intermediates for the synthesis of tetrahydrothienopyridine derivatives, among which the currently more important tetrahydrothienopyridine derivatives are prasugrel (Prasugrel) chemical name 2-acetoxy -5-(a-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine, which is produced by Sankyo of Japan and Eli Lilly of the United States Co-developed drug for the treatment of blood clots. The method for synthesizing tetrahydrothienopyridine derivatives from aromatic cyclopropyl ethyl ketones can refer to the method in patent CN101177430 or patent CN101250193, and the specific route is as follows: [0003] [0004] The method is to use 1-cyclopropyl-2-(2-fluorophenyl) ethyl ketone as a raw material, and carry out bromination reaction wit...

Claims

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Application Information

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IPC IPC(8): C07C45/68C07C49/225C07C49/237C07C49/255C07D495/04
Inventor 高红军李涛车大庆
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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