Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst

A technology of dicarbonyl compounds and gluconate, applied in the preparation of organic compounds, chemical instruments and methods, physical/chemical process catalysts, etc., can solve the problem that chiral ligands and oxidants are expensive and unsuitable for production applications and operations Complicated issues

Inactive Publication Date: 2009-08-12
DALIAN UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] It has been reported in the literature that the use of Davis reagents to obtain chiral α-hydroxy-β-dicarbonyl compounds (Chem.Rev.1992,92,919-934, J.Am.Chem.Soc.2000,122,8453-8463, Org.React.2003, 62, 1-356.), this method is more cumbersome to operate, and the reaction conditions are harsher (-78 ° C ~ 0 ° C, NaHMDS is an alkali), and the oxidant used is an equal or excess chiral oxidant , high cost, not suitable for production application
[0005] Literatu...

Method used

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  • Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst
  • Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst
  • Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst

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Experimental program
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Embodiment 1

[0029] Embodiment 1: Preparation of (-) 5-chloro-1-indanone-2-hydroxyl-2-carboxylic acid methyl ester

[0030] Add 2.24g (10mmol) of methyl 5-chloro-1-indanone-2-carboxylate and 0.58g (1mmol) of homomasine into 160mL of chloroform, stir and dissolve, control the temperature at 15°C, and add tert-butyl peroxide Hydrogen 4.50g (50mmol), the mixture was stirred and reacted, followed by TLC. After the reaction, the reaction solution was washed with 50 mL of 10% aqueous sodium bisulfite solution, the organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under vacuum. The solid product was separated by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 2.21 g of white solid, yield 92%, 65% ee.

[0031] 1 H NMR (400MHz, CDCl 3 )δ 3.24(d, J=17.6Hz, 1H), 3.71(d, J=17.6Hz, 1H), 3.75(s, 3H), 4.04(bs, 1H), 7.42(d, J=8.4Hz, 1H ), 7.50 (s, 1H), 7.74 (d, J=8.4Hz, 1H); MS (API-ES Pos...

Embodiment 2

[0032] Embodiment 2: Preparation of (-) 5-chloro-1-indanone-2-hydroxyl-2-carboxylic acid methyl ester

[0033] Add 2.24g (10mmol) of methyl 5-chloro-1-indanone-2-carboxylate and 1.16g (2mmol) of chloroform into 160mL of chloroform, stir and dissolve, control the temperature at 12°C, add tert-butyl over Hydrogen oxide 4.50g (50mmol), the mixture was stirred and reacted, followed by TLC. After the reaction, the reaction solution was washed with 50 mL of 10% aqueous sodium bisulfite solution, the organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under vacuum. The solid product was separated by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 2.23 g of white solid, yield 93%, 66% ee.

Embodiment 3

[0034] Embodiment 3: Preparation of (-) 5-chloro-1-indanone-2-hydroxyl-2-carboxylic acid methyl ester

[0035] Add 2.24g (10mmol) of methyl 5-chloro-1-indanone-2-carboxylate and 0.29g (0.5mmol) of chloroform into 160mL of chloroform, stir and dissolve, control the temperature at 15°C, add tert-butyl Hydrogen peroxide 4.50g (50mmol), the mixture was stirred and reacted, followed by TLC. After the reaction, the reaction solution was washed with 50 mL of 10% aqueous sodium bisulfite solution, the organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under vacuum. The solid product was separated by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 2.12 g of white solid, yield 89%, 62% ee.

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Abstract

The invention discloses a method for preparing chiral alpha- hydroxyl- beta- dicarbonyl compound by taking lappaconitine as catalyst, belonging to the technical field of organic synthesis. The method is characterized in that beta- dicarbonyl compound, the lappaconitine and oxidizing agent are mixed and stirred in inert solvents for thin layer chromatography trace reaction. After the reaction, the chiral alpha- hydroxyl- beta- dicarbonyl compound is obtained by separation. The inert solvents comprise halogenated hydrocarbon, aromatic hydrocarbon, alkane or the like. The dosage mol ratio between organic peroxide which is taken as the oxidizing agent and the beta- dicarbonyl compound is 1-20, the dosage of the lappaconitine taken as catalyst is 0.5-50mol%, and the reaction temperature is -78 DEG C to 25 DEG C. The lappaconitine is extracted from aconitum sinomontanum in the Middle West part of China, is taken as anodyne and local anaesthetics clinically, and has high safety and no addiction. The new method develops the lappaconitine as organic catalyst, so as to prepare the chiral alpha- hydroxyl- beta- dicarbonyl compound by the anisomerous organic catalyst.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and relates to a method for preparing chiral α-hydroxyl-β-dicarbonyl compounds using quinine as a catalyst. technical background [0002] The optically active α-hydroxyl β-dicarbonyl structure is ubiquitous in natural products and some drug molecules and pesticide molecular structures; at the same time, this structure is also a synthon for the synthesis of other important functional molecular structure intermediates, such as chiral diol compounds. The most ideal way to synthesize chiral α-hydroxy-β-dicarbonyl compounds is chiral catalytic oxidation of β-dicarbonyl compounds. [0003] In recent years, there have been several methods for the preparation of chiral α-hydroxy-β-dicarbonyl compounds. [0004] It has been reported in the literature that the use of Davis reagents to obtain chiral α-hydroxy-β-dicarbonyl compounds (Chem.Rev.1992,92,919-934, J.Am.Chem.Soc.2000,122,8453-8463, Org...

Claims

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Application Information

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IPC IPC(8): C07C69/757C07C67/31B01J31/02
Inventor 孟庆伟宫斌苏田廉明明都健高占先
Owner DALIAN UNIV OF TECH
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