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Method for synthesizing chiral 3-trifluoromethyl-3, 4-dihydroquinoxalinone by palladium-catalyzed asymmetric hydrogenation

A technology for trifluoromethylquinoxalinone and dihydroquinoxalinone is applied in the field of asymmetric hydrogenation synthesis to achieve the effects of high reactivity and enantioselectivity, convenient separation, simple and practical reaction operation

Active Publication Date: 2020-08-04
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
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  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, the synthesis of chiral fluorinated dihydroquinoxalinones is still rarely reported.

Method used

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  • Method for synthesizing chiral 3-trifluoromethyl-3, 4-dihydroquinoxalinone by palladium-catalyzed asymmetric hydrogenation
  • Method for synthesizing chiral 3-trifluoromethyl-3, 4-dihydroquinoxalinone by palladium-catalyzed asymmetric hydrogenation
  • Method for synthesizing chiral 3-trifluoromethyl-3, 4-dihydroquinoxalinone by palladium-catalyzed asymmetric hydrogenation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-8

[0033] Optimization of conditions

[0034] Put palladium trifluoroacetate (0.0025 mmol, 0.85 mg) and chiral ligand (0.003 mmol) into the reaction flask, add 1 ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Then it was concentrated in vacuo, and 3 ml of organic solvent was added under nitrogen, and the solution was transferred to a reaction kettle pre-placed with substrate 1a (27 mg, 0.125 mmol), fed with hydrogen gas at 600 psi, and reacted at 60°C for 48 hours. Release hydrogen slowly, remove solvent and obtain pure product by direct column chromatography separation, change the kind of organic solvent and chiral bisphosphine ligand in the reaction, the temperature of reaction, concrete structure such as table (table 1), reaction formula and coordination The body structure is as follows:

[0035]

[0036] The enantiomeric excess of the product was determined by chiral liquid chromatography, see Table 1.

[0037] Table 1. Asymmetric hydr...

Embodiment 9-23

[0041] Synthesis of Chiral Trifluoromethyldihydroquinoxalinones by Palladium-Catalyzed Asymmetric Hydrogenation 2

[0042] Palladium trifluoroacetate (1.7 mg, 0.0050 mmol) and (R)-SegPhos (3.4 mg, 0.0055 mmol) were put into the reaction flask, 1 ml of acetone was added after nitrogen replacement, and stirred at room temperature for 1 hour. Then concentrate in vacuo, add 3 milliliters of hexafluoroisopropanol under nitrogen, transfer this solution to a reaction kettle with substrate (0.25 mmol) in advance, feed hydrogen to 600 psi, react at room temperature for 48 hours, and slowly release hydrogen , to change the type of reaction substrate, as shown in Table 2. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0043]

[0044] Table 2. Substrate expansion for asymmetric hydrogenation of trifluoromethylquinoxalinones

[0045]

[0046] The corresponding products obtained in Examples 9-23 are resp...

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Abstract

The invention relates to a method for synthesizing chiral 3-trifluoromethyl-3, 4-dihydroquinoxalinone by palladium-catalyzed asymmetric hydrogenation. A catalytic system is a chiral diphosphorus complex of palladium, and the reaction conditions are as follows: the temperature is 0-80 DEG C, the solvent is 2, 2, 2-trifluoroethanol or hexafluoroisopropanol, the pressure ranges from 100 psi to 1000 psi, the ratio of the substrate to the catalyst is 33 / 1, the used metal precursor is palladium trifluoroacetate, and the used chiral ligand is a chiral diphosphorus ligand. The preparation method of the catalyst comprises the following steps: stirring a metal precursor of palladium and a chiral diphosphine ligand in acetone at room temperature, and then carrying out vacuum concentration to obtain the catalyst. Corresponding chiral dihydroquinoxalinone containing trifluoromethyl can be obtained by hydrogenating quinoxalinone containing trifluoromethyl, and the enantiomeric excess of the dihydroquinoxalinone containing trifluoromethyl can reach 99%. The method is simple, convenient and practical to operate, high in enantioselectivity and high in yield, and the reaction has green atom economyand is environmentally friendly.

Description

technical field [0001] The invention belongs to the field of asymmetric hydrogenation synthesis, and in particular relates to the synthesis of chiral trifluoromethyl-3,4-dihydroquinoxaline through the highly enantioselective catalytic hydrogenation of trifluoromethylquinoxalinone using palladium homogeneous system linone method. Background technique [0002] Chiral dihydroquinoxalinones are the core framework of many pesticides, pharmaceutical intermediates and natural products. Therefore, the research on the synthesis and biological activity of this kind of compounds has aroused extensive attention of organic chemists and pharmaceutical circles. The following (formula 1) is the structural unit that the pharmaceutically active molecule contains chiral dihydroquinoxalinone: [0003] [0004] Given the importance of chiral dihydroquinoxalinones and their derivatives in the fields of pharmaceutical and synthetic chemistry, chemists have developed methods to synthesize thes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/44C07D241/38
CPCC07D241/38C07D241/44
Inventor 陈木旺周永贵孙蕾
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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