Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Method for synthesizing 2,3-dihydrobenzofurans compound

A technology of dihydrobenzene and compounds, applied in the direction of steroids, chemical instruments and methods, compounds of group 4/14 elements of the periodic table, etc., which can solve the problems of poor reaction selectivity, poor universality of epoxy substrates, and raw material synthesis Difficulty and other issues

Inactive Publication Date: 2018-07-27
WUHAN UNIV
View PDF3 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are many reports on the synthesis methods of 2,3-dihydrobenzofuran compounds [a) Bertolini, F.; Pineschi, M.Org.Prep.Proced.Int.2009,41,385.b) Sheppard, T.D.J.Chem .Res.2011,35,377.], but starting from simple raw materials, there are few reports on the efficient preparation of 2,3-dihydrobenzofuran compounds
There are two main synthesis methods known at present: the first is to alkylate the phenol at the ortho position, and then add the phenolic hydroxyl group to the double bond to obtain 2,3-dihydrobenzofuran compounds [a) Ohkawa, S.; Fukatsu, K.; Miki, S.; Hashimoto, T.; Sakamoto, J.; Doi, T.; ; Addla, D.; Sridhar, B. Synthesis 2010, 3745.c) Schlgter, J.; Blazejak, M.; Hintermann, L. ChemCatChem2013, 5, 3309.], but the method requires a strong base in the first step, The latter step requires the use of a strong acid; the second is to use 2-(trimethylsilyl)aryl trifluoromethanesulfonate as an aryne precursor for a [3+2] cycloaddition reaction with an epoxy compound Synthesis of 2,3-dihydrobenzofuran compounds [Beltrán-Rodil, S.; D.; Guitián, E.Synlett.2007,1308.], but this method has disadvantages such as difficult synthesis of raw materials, poor reaction selectivity, and poor universality of epoxy substrates

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 synthesizing 2,3-dihydrobenzofurans compound
  • Method for synthesizing 2,3-dihydrobenzofurans compound
  • Method for synthesizing 2,3-dihydrobenzofurans compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Preparation of 7-methyl-2-(phenoxymethyl)-2,3-dihydrobenzofuran-5-carboxylic acid methyl ester

[0052]

[0053] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (2.2mg, 10mol%), XPhos (19.1mg, 20mol%), NBE-CO 2 K (3.5 mg, 10 mol%), methyl 3-methyl-4-iodobenzoate (0.2 mmol, 1.0 equiv.), phenyl glycidyl ether (0.6 mmol, 3.0 equiv.) and dry N-methylpyrrolidone (1.0 mL). The vial was capped and stirred at room temperature for about 5 minutes, after which the mixture was heated to 80°C and stirred for 24 hours. After the reaction vessel was cooled to room temperature, it was quenched with water (10 mL), extracted with methyl tert-butyl ether (3×10 mL), Na 2 SO 4 Dry, filter and concentrate in vacuo. Purified by column chromatography, the eluent is petroleum ether:ethyl acetate=10:1 (v / v), to obtain 7-methyl-2-(phenoxymethyl)-2,3-dihydrobenzofuran - 49 mg of methyl 5-carboxylate (white so...

Embodiment 2

[0054] Example 2: Preparation and gram-level preparation of (R)-7-methyl-2-(benzyloxymethyl)-2,3-dihydrobenzofuran-5-carboxylic acid methyl ester

[0055]

[0056] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (2.2mg, 10mol%), XPhos (19.1mg, 20mol%), NBE-CO 2 K (3.5mg, 10mol%), methyl 3-methyl-4 iodobenzoate (0.2mmol, 1.0equiv.), (R)-benzyl glycidyl ether (0.6mmol, 3.0equiv.) and dry N - Methylpyrrolidone (1.0 mL). The vial was capped and stirred at room temperature for about 5 minutes, after which the mixture was heated to 80°C and stirred for 24 hours. After the reaction vessel was cooled to room temperature, it was quenched with water (10 mL), extracted with methyl tert-butyl ether (3×10 mL), Na 2 SO 4 Dry, filter and concentrate in vacuo. Purified by column chromatography, the eluent is petroleum ether:ethyl acetate=10:1 (v / v), to obtain 7-methyl-2-(benzyloxymethyl)-2,3-dihydrobenzofuran - 58 m...

Embodiment 3

[0058] Example 3: Preparation of 7-methyl-2-(butyryloxymethyl)-2,3-dihydrobenzofuran-5-carboxylic acid methyl ester

[0059]

[0060] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (2.2mg, 10mol%), XPhos (19.1mg, 20mol%), NBE-CO 2 K (3.5 mg, 10 mol%), methyl 3-methyl-4 iodobenzoate (0.2 mmol, 1.0 equiv.), glycidyl n-butyrate (0.6 mmol, 3.0 equiv.) and dry N-methyl Pyrrolidone (1.0 mL). The vial was capped and stirred at room temperature for about 5 minutes, after which the mixture was heated to 80°C and stirred for 24 hours. After the reaction vessel was cooled to room temperature, it was quenched with water (10 mL), extracted with methyl tert-butyl ether (3×10 mL), Na 2 SO 4 Dry, filter and concentrate in vacuo. Purified by column chromatography, the eluent was petroleum ether:ethyl acetate=10:1 (v / v), to obtain 7-methyl-2-(butyryloxymethyl)-2,3-dihydrobenzo 53 mg of methyl furan-5-carboxylate (lig...

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 provides a method for synthesizing a 2,3-dihydrobenzofurans compound. The method comprises the following steps: dissolving aromatic iodide, an epoxy compound, a palladium catalyst, a phosphine ligand and a norborene derivative in an organic solvent together; then carrying out stirring reaction at the temperature of 30-120 DEG C; and carrying out separation and purification after reaction to obtain the 2,3-dihydrobenzofurans compound. By the method, the 2,3-dihydrobenzofurans compound can be synthesized efficiently, economically and environmentally friendly. The method is gentle in condition, good in substrate universality and high in yield, and the prepared 2,3-dihydrobenzofurans compound is widely applied to the fields of medicinal chemistry and organic chemistry.

Description

technical field [0001] The invention relates to a method for synthesizing 2,3-dihydrobenzofuran compounds, belonging to the field of organic synthesis. Background technique [0002] 2,3-Dihydrobenzofuran is an important structural unit widely present in many biologically active natural products and pharmaceutical molecular structures[a) Nichols,D.E.; Hoffman,A.J.; Oberlender,R.A.; Riggs,R.M.J. Med.Chem.1986,29,302.b) Saito, M.; Ueo, M.; Kametaka, S.; Saigo, O.; Uchida, S.; Mori, A.; Ishii, K. Biol. Pharm. Bull. 2008, 31, 1959.c) Huang, Z.; Cui, Q.; Xiong, L.; Wang, Z.; Wang, K.; Zhao, Q.; Bi, F.; Wang, Q.J. Agric. FoodChem. 2009, 57, 2447.d) Lee, I.-S.; Kim, H.-J.; Youn, U.-J.; .-C.; Kim, J.-P.; Ha, D.T.; Ngoc, T.M.; Min, B.-S.; Lee, S.-M.; K.; Bae, K.-H. Helv. Chim. Acta. 2010, 93, 272. e). Radadiya, A; Shah, A. Eur. J. Med. Chem. 2015, 97, 356.]. At present, there are many reports on the synthesis methods of 2,3-dihydrobenzofuran compounds [a) Bertolini, F.; Pineschi, ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/80C07D307/79C07D307/81C07D405/06C07D405/12C07J17/00C07F7/18
CPCC07D307/79C07D307/80C07D307/81C07D405/06C07D405/12C07F7/1892C07J17/00Y02P20/55
Inventor 周强辉吴承贵程鸿刚
Owner WUHAN 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
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