Preparation method of alpha-amino-nitrile compound taking pyrrolidine tertiary amine as primer

A tertiary amine and pyrrolidine technology, which is applied in the field of pharmaceutical intermediates and organic synthesis, can solve the problems of cyanation methods without N-substituted pyrrolidine tertiary amine substrates, and the cyanogen source cannot get rid of toxicity, etc., to achieve High yield, low price, and the effect of overcoming reaction difficulties

Inactive Publication Date: 2019-01-04
求秋平
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the current one-step synthesis of α-aminonitrile has been reported, there is no efficient cyanation method suitable for N-substituted pyrrolidine tertiary amine substrates, and the use of cyanide sources has been unable to get rid of the problem of toxicity

Method used

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  • Preparation method of alpha-amino-nitrile compound taking pyrrolidine tertiary amine as primer
  • Preparation method of alpha-amino-nitrile compound taking pyrrolidine tertiary amine as primer
  • Preparation method of alpha-amino-nitrile compound taking pyrrolidine tertiary amine as primer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] S1: Add 60ml of trifluoroethanol-dichloromethane mixed organic solvent (trifluoroethanol:dichloromethane=36ml:24ml) and tertiary amine raw material N-phenylpyrrolidine 10mmol, Cu(OTf) 2 - Copper acetate composite catalyst 2mg (wherein Cu(OTf) 2 1.2mg), in the presence of 8mmol sodium tert-butoxide, mix and stir at room temperature for 10min, and gradually raise the temperature to 60°C;

[0055] S2: Add 30mmol cyanide potassium ferrocyanide K 4 Fe(CN) 6 , and 5mmol of the p-trifluoromethyl iodobenzene derivative as a reaction accelerator, nitrogen replacement to remove the air in the reaction system, keep the temperature, fully react under stirring conditions, and use TLC to detect the reaction; wherein, the The structure of trifluoromethyl iodobenzene derivatives is as follows:

[0056]

[0057] S3: after 5h, the reaction is complete, cooled to room temperature, the reaction system is suction filtered to remove the catalyst, the filter cake is washed with dichlor...

Embodiment 2

[0061] S1: Add 100ml trifluoroethanol-dichloromethane mixed organic solvent (trifluoroethanol:dichloromethane=70ml:30ml) and N-phenylpyrrolidine 20mmol, Sc(OTf) respectively in the round bottom flask equipped with stirring 3 -Copper acetate composite catalyst 3mg (wherein Sc(OTf) 3 2mg), in the presence of 16mmol potassium tert-butoxide, mixed and stirred at room temperature for 5min, and gradually raised the temperature to 70°C;

[0062] S2: Add 60mmol cyanide potassium ferrocyanide K 4 Fe(CN) 6 , and 15mmol of 2-iodo-5-cyanotrifluorotoluene as a reaction accelerator, nitrogen replacement to remove the air in the reaction system, keep the temperature, fully react under stirring conditions, and proceed with the TLC detection reaction;

[0063] S3: After the reaction is completed, cool to room temperature, remove the catalyst by suction filtration of the reaction system, wash the filter cake with dichloromethane, collect the combined filtrate, remove the solvent under reduce...

Embodiment 3

[0065] S1: Add 100ml trifluoroethanol-dichloromethane mixed organic solvent (trifluoroethanol:dichloromethane=70ml:30ml) and N-benzylpyrrolidine 20mmol, Cu(OTf ) 2 - 4 mg of indium triiodide composite catalyst (wherein Cu(OTf) 2 3mg), in the presence of 20mmol potassium tert-butoxide, mixed and stirred at room temperature for 5min, and gradually raised the temperature to 60°C;

[0066] S2: Add 60mmol cyanide potassium ferrocyanide, and 20mmol of 2-iodo-5-cyanotrifluorotoluene as a reaction accelerator, replace with nitrogen to remove the air in the reaction system, keep the temperature, under stirring After fully reacting for about 6 hours, the reaction is basically over;

[0067] S3: After the reaction is completed, cool to room temperature, remove the catalyst by suction filtration of the reaction system, wash the filter cake, collect the combined filtrate, remove the solvent under reduced pressure, and separate using silica gel column chromatography (eluent is V (petrole...

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Abstract

The invention provides a preparation method of an alpha-amino-nitrile compound taking pyrrolidine tertiary amine as a primer. The preparation method comprises the following step of green synthesis ofalpha-amino-nitrile through a one-pot process by taking potassium ferrocyanide as a cyaniding reagent and an iodine phenyl compound as a reaction accelerant under the condition of a compound solvent containing trifluoroethanol and a catalyst. The invention provides the safer cyaniding reagent and an efficient synthetic method of alpha-amino-nitrile with mild reaction conditions. The preparation method is simple in post treatment, mild in reaction condition and short in reaction time, and develops a simple and efficient synthetic route for cyaniding synthesis of pyrrolidine tertiary amine.

Description

technical field [0001] The invention relates to a preparation method of α-aminonitrile, in particular to a preparation method of an α-aminonitrile compound with N-substituted pyrrolidine tertiary amine as a substrate, and belongs to the fields of pharmaceutical intermediates and organic synthesis. Background technique [0002] α-Aminonitrile is a very important intermediate in organic synthesis, and has important applications in pharmaceutical synthesis, pesticide synthesis, and in vivo transformation. It can synthesize amino acids, amides and some nitrogen-containing heterocyclic compounds, among which α-amino acid is an important component of protein construction, and also plays a very important role in the fields of pharmaceuticals, natural products, medicine, and bioengineering. In view of this, the development of effective α-aminonitrile synthesis methods has been the focus of attention in this field. [0003] Among the currently reported methods for the synthesis of α...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/16B01J27/26
CPCB01J27/26C07D207/16
Inventor 求秋平
Owner 求秋平
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