Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Alpha-keto ester compound with gamma chiral center and synthetic method thereof

A synthetic method and technology of keto esters, applied in the direction of organic chemical methods, preparation of organic compounds, chemical instruments and methods, etc., to achieve good application prospects, good application effects, simple and safe operation

Inactive Publication Date: 2012-09-19
SHANGHAI JIAO TONG UNIV +1
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The α-hydroxyphenylbutyric acid structure is an important skeleton in the structure of pril-like drugs, and the improvement and derivation of this skeleton is an important method for the development of pril-like drugs, and it can be composed of γ-substituent β, γ-unsaturated α -Ketoester compounds are further derived. The previous modification methods are all modified from one side of the peptide, and there has never been a report of chiral modification from the γ-position of the backbone.

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
  • Alpha-keto ester compound with gamma chiral center and synthetic method thereof
  • Alpha-keto ester compound with gamma chiral center and synthetic method thereof
  • Alpha-keto ester compound with gamma chiral center and synthetic method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The catalytic product 3a (R 2 = Me,R 1 =Ph) Preparation

[0033] 5mL reaction flask, add copper acetate monohydrate (0.005mmol) and ligand L3 (0.01mmol), N 2For protection, add 1 mL of dry toluene, stir and coordinate at room temperature for 3 hours, dissolve the substrate γ-phenyl β, γ-unsaturated α-keto acid methyl ester (0.25 mmol) in 1 mL of dry toluene and add dropwise to the reaction system and stir for 5 minute. Diethylzinc (0.375 mmol, 1.0 M in n-hexane) was slowly added dropwise. The system was reacted at 26°C, and the reaction was monitored by thin-layer chromatography (hereinafter referred to as "TLC"). After the reaction was completed for 2 hours, a saturated solution of ammonium chloride was added to quench, and ethyl acetate (5ml×3) extracted , dried over anhydrous magnesium sulfate, filtered and concentrated. Ethyl acetate / petroleum ether=1:10 The product 3a was obtained by column chromatography with a yield of 81% and corresponding selectivity of 58...

Embodiment 2

[0038] The catalytic product 3a (R 2 = Me,R 1 =Ph) Preparation

[0039] 5mL reaction flask, add copper acetate monohydrate (0.005mmol) and ligand L3 (0.01mmol), N 2 For protection, add 1 mL of dry toluene, stir and coordinate at room temperature for 3 hours, dissolve the substrate γ-phenyl β, γ-unsaturated α-keto acid methyl ester (0.25 mmol) in 1 mL of dry toluene and add dropwise to the reaction system and stir for 5 minute. Diethylzinc (0.375 mmol, 1.0 M in n-hexane) was slowly added dropwise. The system was reacted at -20°C, and the reaction was monitored by TLC. The reaction was completed for 2 hours, quenched by adding a saturated solution of ammonium chloride, extracted with ethyl acetate (5ml×3), dried over anhydrous magnesium sulfate, filtered, and concentrated. Ethyl acetate / petroleum ether=1:10 The product obtained by column chromatography has a yield of 88% and a corresponding selectivity of 68%.

Embodiment 3

[0041] The catalytic product 3a (R 2 = Me,R 1 =Ph) Preparation

[0042] 5mL reaction flask, add copper acetate monohydrate (0.005mmol) and ligand L3 (0.01mmol), N 2 For protection, add 1 mL of dry toluene, stir and coordinate at room temperature for 3 hours, dissolve the substrate γ-phenyl β, γ-unsaturated α-keto acid methyl ester (0.25 mmol) in 1 mL of dry toluene and add dropwise to the reaction system and stir for 5 minute. Diethylzinc (0.375 mmol, 1.0 M in n-hexane) was slowly added dropwise. The system was reacted at -30°C, and the reaction was monitored by TLC. After 2 hours of reaction, a saturated solution of ammonium chloride was added to quench, extracted with ethyl acetate (5ml×3), dried over anhydrous magnesium sulfate, filtered, and concentrated. Ethyl acetate / petroleum ether=1:10 The product obtained by column chromatography has a yield of 99% and a corresponding selectivity of 65%.

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 relates to a novel alpha-keto ester compound with a gamma chiral center and a synthetic method of the alpha-keto ester compound. The synthetic method comprises the following steps of: enabling zinc dialkyl and a beta, gamma-unsaturated alpha-keto ester compound shown as the structural formula (2) (see the accompanying diagram) to perform asymmetrical 1, 4-conjugate reaction in the present of the catalyst generated by chiral phosphoramidite ligand and copper salt; and generating the alpha-keto ester compound with the gamma chiral center shown as the structural formula (1) (see the accompanying diagram), wherein R1 is any one of naphthenic base, aryl, substitute aryl, aralkyl and heteroaryl, R2 is any one of straight-chain or branched-chain alkyl with 1-6 carbon atom(s) and aralkyl, and R3 is alkyl.

Description

technical field [0001] The invention relates to a novel α-ketoester compound with a γ-position chiral center and a synthesis method thereof. Background technique [0002] In asymmetric catalytic reactions, asymmetric 1,4-conjugate addition is the selective attack of nucleophiles on carbocations in 1,4-unsaturated compounds to form new carbon-carbon bonds and obtain Chiral carbon atoms, this reaction is an extremely important method for building chiral carbon-carbon bonds. After searching the existing technical literature, among the existing ligands, the phosphoramidite ligands, especially the axial chiral phosphoramidite ligands, have excellent effects in the asymmetric 1,4-conjugated addition reaction (a.De Vries, A.H.M.; Meetsma, A.; Feringa, B.L. Angew. Chem., Int. Ed. 1996, 35, 2374-2376.b. Hua, Z.; Vassar, V.C.; Choi, H.; . Natl. Acad. Sci. U.S.A. 2004, 101, 5411. c. Alexakis, A.; Rosset, B.S.; Humam, M. J. Am. Chem. Soc. 2002, 124, 5262.). In 2010, the D2-symmetric ...

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): C07B53/00C07C69/738C07C67/347C07C205/56C07C201/12C07D307/54
Inventor 张万斌谢芳杨波
Owner SHANGHAI JIAO TONG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com