Method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylic ester and application

A dynamic kinetics, technology of alkyl carboxylate, applied in the direction of organic chemical method, carboxylate/lactone preparation, reaction preparation of ester group and hydroxyl group, etc.

Pending Publication Date: 2021-07-16
HENAN NORMAL UNIV
View PDF8 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nucleophilic sites in previously reported catalysts are limited to nitrogen or carbon atoms, wh

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylic ester and application
  • Method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylic ester and application
  • Method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylic ester and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023]

[0024]

[0025] [a] Unless otherwise stated, the reaction conditions are as follows: ester (0.05mmol), 2a (18.4mg, 0.1mmol), catalyst C9f (2.2mg, 0.005mmol, 10mol%), iPr 2 EtN (17.4 μL, 0.1 mmol) was placed in DCM (0.5 mL) for 72 hours. [b] NMR yield. [c] Determined by chiral HPLC analysis. N.R = no response.

[0026] Taking pentafluorophenol ester 1b and benzhydryl alcohol 2a as raw materials to generate 3a as an example, the reaction conditions were optimized, and the reaction equation was as follows:

[0027]

[0028] The specific reaction results are shown in the following table:

[0029]

[0030] [a] Reaction conditions: 1 (0.05mmol), 2a (0.1mmol), catalyst (10mol%) and base (2equiv) react in solvent (0.5mL) for 72h. [b] NMR yield. [c] Determined by chiral HPLC analysis. [d] PhCF 3 / DCM(1 / 1,v / v).[e]Et 3 N(5equiv), PhCF 3 / DCM(1 / 1,v / v).[f]1b(0.2mmol),2a(0.4mmol),C9f(10mol%),andEt 3 N(5equiv)in PhCF 3 / DCM (0.5mL, 1 / 1, v / v) for 72h. [g] C9f (5...

Embodiment 2

[0034] In a dry 5mL reaction tube, add chiral catalyst C9f (8.8mg, 0.02mmol, 10mol%), benzhydryl alcohol 2a (73.6mg, 0.4mmol) and pentafluorophenol ester 1b-l (0.2mmol) respectively, and then Trifluorotoluene / dichloromethane (1 / 1, v / v, 0.5 mL) was added, and finally triethylamine (152 μL, 1 mmol) was added, and the reaction solution was stirred at 0° C. for 72 hours. After the reaction was completed, the product was obtained after column chromatography.

[0035] The specific results are as follows:

[0036]

[0037]

[0038] Representative NMR characterization data are as follows:

[0039] (S)-Benzhydryl-2-(o-tolyl) propanoate (3c)

[0040]

[0041] Colorless oil, 55.5mg, 84% yield, 95% ee; R f=0.38(Pet / EtOAc, 10 / 1, v / v).HPLCCHIRALCEL ID, n-hexane / 2-propanol=90 / 10, flow rate=0.6mL / min, λ=256nm, retention time: 9.060min(minor ),9.478min(major).[α] D 21 =+33.4 (c=2.0, CHCl 3 ); 1 HNMR (400MHz, CDCl 3 )δ7.32–7.22(m,5H),7.21–7.09(m,7H),7.06–7.00(m,2H),6.83(s,1H),...

Embodiment 3

[0061]

[0062] In a dry 5mL reaction tube, add chiral catalyst C9f (8.8mg, 0.02mmol, 10mol%), benzhydryl alcohol 2a (73.6mg, 0.4mmol) and pentafluorophenol ester 1m (74.4mg, 0.2mmol), Then trifluorotoluene / dichloromethane (1 / 1, v / v, 0.5 mL) was added, and finally triethylamine (152 μL, 1 mmol) was added, and the reaction solution was stirred at 0° C. for 72 hours. Column chromatography separated to obtain 66.2mg of colorless oil 3m, yield 89%, 90% ee. HPLC CHIRALCEL IA, n-hexane / 2-propanol=99 / 1, flow rate=0.5mL / min, λ=256nm, retention time: 27.917min(major), 33.453min(minor)[α] D 21 =+20.5 (c=1.40, CHCl 3 ). 1 H NMR (400MHz, CDCl 3 )δ7.32-7.21(m,5H),7.21-7.14(m,5H),7.11-7.03(m,4H),6.81(s,1H),3.80(q,J=7.2Hz,1H),2.46 (d,J=7.2Hz,2H),1.89-1.82(m,1H),1.51(d,J=7.2Hz,3H),0.91(d,J=7.2Hz,6H).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylic ester and application, and belongs to the technical field of organic synthesis. Pentafluorophenol ester and benzhydrol are taken as reactants, a dynamic kinetic resolution reaction is carried out under the nitrogen-oxygen catalysis of chiral DMAP derived from diphenylmethylamine to obtain alpha-aryl-alpha-alkyl ester, and (S)-naproxen, (S)-ibuprofen, (S)-ketoprofen, (S)-fenopolfen and (S)-flurbiprofen are synthesized. According to the chiral DMAP nitrogen-oxygen catalyst, oxygen atoms in pyridine nitrogen-oxygen serve as nucleophilic sites to participate in a dynamic kinetic resolution reaction, and meanwhile hydrogen in catalyst molecules also plays a key role. The method has the advantages of good yield, high enantioselectivity and the like.

Description

technical field [0001] The invention relates to a method for dynamic kinetic resolution of α-aryl-α-alkyl carboxylate catalyzed by a chiral DMAP nitrogen-oxygen catalyst, which belongs to the technical field of asymmetric synthesis in organic chemistry. Background technique [0002] Optically active α-aryl-α-alkylcarboxylic acids and their derivatives are important bioactive molecules, such as (S)-ibuprofen, (S)-naproxen, (S)-ketoprofen, (S)-Fenoprofen and (S)-Frorbinofine are widely used NSAIDs. Nucleophilic sites in previously reported catalysts are limited to nitrogen or carbon atoms, and the use of oxygen atoms as nucleophilic sites has not been applied to this type of reaction. [0003] Therefore, it is of great research significance to develop efficient synthetic methods to prepare chiral α-aryl-α-alkylcarboxylic acids and their derivatives. Contents of the invention [0004] In order to solve the above technical problems, the present invention discloses a method f...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C69/612C07C67/03C07C69/734C07C69/65C07C59/64C07C51/09C07C57/30C07C59/84C07C59/68C07C57/58
CPCC07C67/03C07C51/09C07B2200/07C07C69/612C07C69/734C07C69/65C07C59/64C07C57/30C07C59/84C07C59/68C07C57/58
Inventor 谢明胜连赛雅李宁武晓霞渠桂荣郭海明
Owner HENAN NORMAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap