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A kind of palladium-catalyzed quinoline-3-amine asymmetric hydrogenation method for the synthesis of chiral exocyclic amines

A chiral exocyclic amine and quinoline-catalyzed technology, which is applied in chemical instruments and methods, physical/chemical process catalysts, organic compound/hydride/coordination complex catalysts, etc., can solve the problem of strong coordination ability, aromatic amine Low activity, catalyst poisoning and other problems, to achieve the effect of complete reaction, convenient preparation and simple reaction operation

Active Publication Date: 2017-10-03
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on the asymmetric hydrogenation of aromatic amines, mainly due to the low activity and strong coordination ability of aromatic amines, which easily lead to catalyst poisoning.

Method used

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  • A kind of palladium-catalyzed quinoline-3-amine asymmetric hydrogenation method for the synthesis of chiral exocyclic amines
  • A kind of palladium-catalyzed quinoline-3-amine asymmetric hydrogenation method for the synthesis of chiral exocyclic amines
  • A kind of palladium-catalyzed quinoline-3-amine asymmetric hydrogenation method for the synthesis of chiral exocyclic amines

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Experimental program
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Effect test

Embodiment 1

[0028] Example 1: Palladium-catalyzed asymmetric hydrogenation of quinolin-3-amine to synthesize various chiral exocyclic amine compounds

[0029] Put palladium trifluoroacetate (0.005 mmol) and (S)-L (0.006 mmol) into the reaction flask, add 1 ml of acetone after nitrogen replacement, stir at room temperature for 1 hour, and then concentrate in vacuo to remove acetone to obtain a catalyst. In the glove box, dissolve the prepared catalyst in dichloromethane and transfer it to another reaction flask containing the substrate (0.10 mmol) and trifluoroacetic acid (0.06 mmol) in advance, sharing 4 ml of dichloromethane. After stirring for 5 minutes, the reaction flask was put into a stainless steel autoclave, hydrogen gas (1000 psi) was introduced, and the reaction was carried out at 70°C (or 80°C) for 18 hours. Slowly release hydrogen, stir with 5ml saturated sodium bicarbonate at room temperature for 10 minutes to make it alkaline, remove the activator acid, extract with dichloromet...

Embodiment 2

[0045] Example 2: Synthesis of a substance P antagonist 4

[0046] Under the protection of nitrogen, add hydrazine hydrate (2.00 mmol) to the ethanol solution dissolved in 2k (0.10 mmol), and then react at 60°C. After the reaction is complete, spin off the solvent. Use 10mL dichloromethane and 10mL for the remaining solids. The aqueous solvent is separated. The aqueous phase is extracted with dichloromethane. The organic phases are combined, dried over anhydrous sodium sulfate, filtered, spin-dried, combined organic phases, dried over anhydrous sodium sulfate, filtered, and the solvent is removed by rotary evaporation. Column chromatography The pure product 3 is isolated.

[0047] Under the protection of nitrogen, compound 3 (0.10 mmol) and NaBH(OAc) 3 (0.30 mmol) was dissolved in 2 mL of 1,2-dichloroethane, and then 1 mL of 1,2-dichloroethane solution with o-methoxybenzaldehyde (0.11 mmol) was added dropwise to it, and then heated at 50°C After the reaction is complete, use satur...

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Abstract

A method for palladium-catalyzed asymmetric hydrogenation of quinoline-3-amine to synthesize chiral exocyclic amines is characterized in that Bronsted acid is used as an activator, and the catalytic system used is a chiral bisphosphine complex of palladium. Reaction can be carried out under following conditions, reaction temperature: 60-80 ℃; Reaction adopts solvent: methylene chloride; Hydrogen pressure: 20-70 atmospheric pressure; The molar ratio of substrate and catalyst is 20 / l; Used metal precursor : palladium trifluoroacetate (Pd(OCOCF3)2); chiral ligand used: chiral bisphosphine ligand; activator used: trifluoroacetic acid (CF3CO2H). For quinoline-3-amine, the corresponding chiral exocyclic amine derivative can be obtained, and its enantiomeric excess value can reach 90%. The invention has the advantages of simple and convenient operation, readily available raw materials, good enantioselectivity, high yield, and the reaction has green atom economy and is environmentally friendly.

Description

Technical field [0001] The invention relates to a method for synthesizing chiral exocyclic amines by using a homogeneous system of palladium to catalyze the hydrogenation of quinolin-3-amine with high enantioselectivity. Background technique [0002] Chiral exocyclic amines are a kind of reaction intermediates commonly used in organic synthesis. In addition, this structure exists in many biologically active natural or non-natural compounds. In recent decades, they have also been used as very effective chiral organic catalysts or ligands in a series of chemical reactions. [0003] Because such compounds play an important role in the fields of medicine and synthetic chemistry, the research on the synthetic methods of such compounds has become a hot spot (Document 1: a) Xie, J.-H.; Zhu, S.-F.; Zhou, Q .-L.Chem.Rev.2011,111,1713; b) Nugent, TC Chiral Amine Synthesis, Wiley-VCH, Weinheim, 2010; c) Trost, BM; Crawley, MLChem. Rev. 2003, 103, 2921; d) Müller, TE; Hultzsch, KC; Yus, M.; ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/54B01J31/24
CPCC07D215/38
Inventor 周永贵蔡先锋郭冉柠时磊
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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