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Preparation method of optical pure alpha-hydroxyl-beta-aminopropionic acid ester derivative

A technology of aminopropionate and derivatives, which is applied in the field of preparation of α-hydroxy-β-alanine ethyl derivatives, can solve the problems of unfavorable industrial production and high production costs, and achieve the improvement of technical cost and production efficiency, and easy The effect of stable operation and performance

Inactive Publication Date: 2013-04-17
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current synthetic method has the following disadvantages: a multi-step synthesis method is required to obtain optically pure α-hydroxyl-β-alanine derivatives; alkyl-substituted α-hydroxyl-β-alanine derivatives The synthesis still needs to use equivalent chiral reagent; The production cost is high, is unfavorable for industrialized production

Method used

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  • Preparation method of optical pure alpha-hydroxyl-beta-aminopropionic acid ester derivative
  • Preparation method of optical pure alpha-hydroxyl-beta-aminopropionic acid ester derivative
  • Preparation method of optical pure alpha-hydroxyl-beta-aminopropionic acid ester derivative

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Example 1 Preparation of (2S, 3S)-2-hydroxyl-3-anilinophenylpropionic acid ethyl ester

[0029] Weigh N-phenylbenzaldimine (1.0mmol), rhodium acetate (0.01mol), (R)-3,3'-(ditriphenylsilyl)-binaphthol phosphoric acid (0.02mol), Add it into a 20mL two-necked bottle, add commercially available reagent grade solvent dichloromethane, stir and configure a mixed solution with a total amount of 8mL, that is, make a mixed solution of imine, rhodium acetate, water and solvent. Measure water (2.0mmol) with a micro-injector, inject it into a two-neck bottle, stir well and mix evenly. Weigh ethyl diazoacetate (2.0mmol), add dichloromethane to make 4mL mixed solution (diazo solution), draw the mixed solution with a 5mL syringe, inject the diazo solution into the diazo solution for 1 hour by peristaltic pump control In the dichloromethane solution of amine, rhodium acetate and water, after stirring at room temperature for 1 hour, the dichloromethane was removed by rotary evaporation ...

Embodiment 2

[0031] Example 2 Preparation of (2S, 3S)-2-methyl-2-hydroxyl-3-anilinophenylpropionic acid isopropyl ester

[0032] Weigh N-phenylbenzaldimine (1.0mmol), rhodium acetate (0.01mol), (R)-3,3'-(ditriphenylsilyl)-binaphthol phosphoric acid (0.02mol), Add it to a 20mL two-necked bottle, add commercially available reagent grade dichloromethane, and stir to form a mixed solution with a total volume of 8mL. Measure water (2.0mmol) with a micro-injector, inject it into a two-neck bottle, stir well and mix evenly. Weigh isopropyl diazopropionate (2.0mmol), add dichloromethane to form a 4mL mixed solution, draw the mixed solution with a 5mL syringe, and inject imine, rhodium acetate and water dichloromethane via a peristaltic pump control for 1 hour. In the methane solution, after stirring at room temperature for 1 hour, dichloromethane was removed by rotary evaporation at 40°C, and then the pure target product 1b was isolated by column chromatography (eluent: petroleum ether: ethyl ace...

Embodiment 3

[0034] Example 3 Preparation of (2S, 3S)-2-methyl-2-hydroxyl-3-anilinophenylpropionic acid ethyl ester

[0035] Weigh N-phenylbenzaldimine (1.0mmol), dichlorobis(4-isopropyltoluene) staple (0.01mol) (R)-3,3'-(ditriphenylsilyl)- Add binaphthol phosphoric acid (0.02mol) into a 20mL two-necked bottle, add commercially available reagent grade dichloromethane, and stir to form a mixed solution with a total volume of 8mL. Measure water (2.0mmol) with a micro-injector, inject it into a two-neck bottle, stir well and mix evenly. Weigh ethyl diazopropionate (2.0mmol), add dichloromethane to make 4mL mixed solution, draw the mixed solution with a 5mL syringe, and inject the dichloromethane of imine, rhodium acetate and water by peristaltic pump control for 1 hour. In the solution, after stirring at room temperature for 1 hour, dichloromethane was removed by rotary evaporation at 40°C, and then the pure target product 1c was isolated by column chromatography (eluent: petroleum ether: et...

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Abstract

The invention discloses a preparation method of an optical pure alpha-hydroxyl-beta-aminopropionic acid ester derivative, which comprises the steps of taking imine, water and diazonium as raw materials, taking lewis acid and chiral bronsted acid as catalysts, conducting a co-catalytic one-step reaction, and obtaining the alpha-hydroxyl-beta-aminopropionic acid ester derivative as shown in Formula (I). According to the method, a high atom economical reaction is adopted to prepare the alpha-hydroxyl-beta-aminopropionic acid ester derivative with high yield and stereoselectivity, and the method has the advantages that the method is short in synthetic route, involves only one step, and is simple to operate.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and relates to a method for preparing alpha-hydroxy-beta-alanine ethyl derivatives. Background technique [0002] α-Hydroxy-β-alanine derivatives are a very important structural unit, which widely exist in physiologically active compounds and natural products. For example, anticancer drug paclitaxel, HIV virus inhibitor (KNI)-227, besistatin, aminoprotease inhibitor Leuhistin, etc. [0003] [0004] α-Hydroxy-β-alanine ethyl ester derivatives are widely used in asymmetric catalytic synthesis as chiral ligands and auxiliary reagents in organic synthesis methodology (Chem.Rev.1996,96,835).Whitesell,J , K; Meyers.A.IWhitesell, J.K; Whitesell, M.A. et al. have reported using α-hydroxy-β-amino compounds to assist the asymmetric alkylation of cyclohexanone, and the ee value can reach 95%. Yamaguchi, S; Brinkmeyer, R.S (J.Am.Chem.Soc.1976, 98, 3032) and others have used th...

Claims

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Application Information

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IPC IPC(8): C07C227/10C07C229/34C07D307/54C07B53/00
Inventor 胡文浩史滔达荆常诚
Owner EAST CHINA NORMAL UNIVERSITY
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