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Method for synthesizing chiral cyclohexanediamine through asymmetric hydrogenation of palladium-catalyzed quinoline-3-amine

A chiral exocyclic amine, catalyzing quinoline technology, 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 amines Low activity, catalyst poisoning and other problems, to achieve the effect of complete reaction, convenient preparation and simple reaction operation

Active Publication Date: 2015-11-04
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • Method for synthesizing chiral cyclohexanediamine through asymmetric hydrogenation of palladium-catalyzed quinoline-3-amine
  • Method for synthesizing chiral cyclohexanediamine through asymmetric hydrogenation of palladium-catalyzed quinoline-3-amine
  • Method for synthesizing chiral cyclohexanediamine through asymmetric hydrogenation of palladium-catalyzed quinoline-3-amine

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Example 1: Synthesis of various chiral exocyclic amine compounds by palladium-catalyzed asymmetric hydrogenation of quinoline-3-amine

[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, then concentrate in vacuo to remove acetone to obtain a catalyst. In the glove box, the prepared catalyst was dissolved in dichloromethane, and then transferred to another reaction flask with substrate (0.10 mmol) and trifluoroacetic acid (0.06 mmol) in advance, sharing 4 ml of dichloromethane. After stirring for 5 minutes, the reaction bottle 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 the hydrogen gas, stir with 5 ml of saturated sodium bicarbonate at room temperature for 10 minutes to make it alkaline, remove the activator acid, extr...

Embodiment 2

[0045] Embodiment 2: the synthesis of a kind of 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, and use 10 mL dichloromethane and 10 mL Water solvent, liquid separation, aqueous phase extracted with dichloromethane, combined organic phases, dried over anhydrous sodium sulfate, filtered, spin-dried, combined organic phases, dried over anhydrous sodium sulfate, filtered and then rotary evaporated to remove solvent, column chromatography Pure product 3 was isolated.

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

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Abstract

The invention discloses a method for synthesizing chiral cyclohexanediamine through asymmetric hydrogenation of palladium-catalyzed quinoline-3-amine. The method is characterized in that bronsted acid is used as an activating agent, and a catalytic system used in the method is a chiral biphosphine complex of palladium. The reaction can be carried out under the following conditions: the reaction temperature ranges from 60 DEG C to 80 DEG C; dichloromethane is used as a reaction reagent; the hydrogen pressure is 20-70 atmospheres; the molar ratio of a substrate to a catalyst is 20:1; palladium trifluoroacetate (Pd(OCOCF3)2) is used as a metal precursor; a chiral biphosphine ligand is used as a chiral ligand; and trifluoroacetic acid (CF3CO2H) is used as an activating agent. Corresponding chiral cyclohexanediamine derivatives can be prepared from quinoline-3-amine, and the enantiomeric excess can be up to 90%. The method is simple and convenient to operate, available in raw material, good in enantioselectivity, high in yield, capable of realizing green atom economy in reaction and environment-friendly.

Description

technical field [0001] The invention relates to a method for synthesizing chiral exocyclic amines through the highly enantioselective catalytic hydrogenation of quinoline-3-amines in a palladium homogeneous system. Background technique [0002] Chiral exocyclic amines are a class of reaction intermediates commonly used in organic synthesis. In addition, there are many natural or non-natural compounds with biological activity. In recent decades, they have also been used as very effective chiral organic catalysts or ligands in a series of chemical reactions. [0003] Because this kind of compound plays an important role in the fields of medicine and synthetic chemistry, the research on the synthesis method of this kind of compound has become a hot spot (Document 1: a) Xie, J.-H.; Zhu, S.-F.; Zhou, Q .-L.Chem.Rev.2011, 111, 1713; b) Nugent, T.C. Chiral Amine Synthesis, Wiley-VCH, Weinheim, 2010; c) Trost, B.M.; Crawley, M.L.Chem.Rev.2003, 103, 2921; d) Müller, T.E.; Hultzsch,...

Claims

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Application Information

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Patent Type & Authority Applications(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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