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

Synthesis method of 2-trifluoromethyloxazole derivatives

A technology for trifluoromethyl oxazoles and a synthesis method, applied in the field of synthesis of 2-trifluoromethyl oxazole derivatives, can solve the problems of difficult preparation of raw materials, high synthesis cost, single substitution type, etc. Gentle, easy-to-use effect

Inactive Publication Date: 2011-11-16
TIANJIN UNIV
View PDF0 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The above method for synthesizing 2-trifluoroacetoxy oxazole usually has disadvantages such as difficult preparation of raw materials, high synthesis cost, and single substitution type, and most of them use corrosive trifluoroacetic acid or trifluoroacetic anhydride as a fluorine source to introduce three Fluoromethyl
In all these synthetic methods, it has not yet been seen that the simple and easy-to-obtain β-position unsubstituted enamine compound (II) is used as a substrate, and a non-toxic and environmentally friendly solid reagent, i.e. bis(trifluoroacetoxy) iodine Benzene is used as a fluorinating reagent to prepare 2-trifluoromethyloxazole compounds

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
  • Synthesis method of 2-trifluoromethyloxazole derivatives
  • Synthesis method of 2-trifluoromethyloxazole derivatives
  • Synthesis method of 2-trifluoromethyloxazole derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preparation of 2-trifluoromethyl-4-phenyl-5-methoxycarbonyloxazole (I-a):

[0032]

[0033] Bis(trifluoroacetoxy)iodobenzene (0.243 g, 0.0006 mol) was dissolved in dry 1,2-dichloroethane (6 mL), stirred and heated to 40°C. Dissolve methyl 3-amino-3-phenylacrylate (II-a) (0.1g, 0.0006mol) in dry 1,2-dichloroethane (12mL) and add dropwise to the above solution within 8 minutes , stirred at 45°C for 1 h until the reaction was complete, the solution was added to silica gel (0.12 g) and evaporated to dryness, separated by column chromatography (ethyl acetate: petroleum ether = 1:99) to obtain 0.104 g of white crystals, with a yield of 73%. Melting point: 47-48°C.

[0034] 1 H-NMR (CDCl 3 , 400MHz) δ: 8.11-8.12 (m, 2H), 7.50-7.51 (m, 3H), 4.00 (s, 3H). 13 C-NMR (CDCl 3 , 100MHz) δ: 157.93(C), 150.07~150.40(q, J C-F =45Hz, C), 146.85(C), 137.83(C), 130.52(C), 129.36(CH), 128.49(CH), 128.40(CH), 114.71~117.41(q, J C-F =270Hz, CF 3 ), 52.76 (OCH 3 ). 19 F-NMR (CDCl ...

Embodiment 2

[0036] Preparation of 2-trifluoromethyl-4-p-bromophenyl-5-methoxycarbonyloxazole (I-b):

[0037]

[0038]Bis(trifluoroacetoxy)iodobenzene (0.174 g, 0.0004 mol) was dissolved in dry anhydrous dichloromethane (4 mL), stirred at 40°C until constant temperature. Dissolve 3-amino-3-p-bromophenylmethylacrylate (II-b) (0.1g, 0.0004mol) in dry anhydrous dichloroethane (8mL) and add dropwise to the above solution within 8 minutes , stirred at 50°C for 1.5h until the reaction was complete, the solution was added to silica gel (0.12g) and evaporated to dryness, separated by column chromatography (ethyl acetate:petroleum ether=1:99) to obtain 0.078g of white solid, yield 58%. Melting point: 74-75°C.

[0039] 1 H-NMR (CDCl 3 , 400MHz) δ: 8.03~8.05 (d, 2H, J=8.4Hz), 7.60~7.63 (d, 2H, J=8.8Hz), 4.00 (s, 3H). 13 C-NMR (CDCl 3 , 100MHz) δ: 157.84(C), 150.52~150.96(q, J C-F =45Hz, C), 145.79(C), 137.93(C), 131.67(C), 130.87(CH), 127.36(CH), 125.18(C), 114.61~117.32(q, J C-F =270Hz, CF...

Embodiment 3

[0041] Preparation of 2-trifluoromethyl-4-o-methoxyphenyl-5-methoxycarbonyloxazole (I-c):

[0042]

[0043] Bis(trifluoroacetoxy)iodobenzene (0.229 g, 0.0005 mol) was dissolved in dry 1,2-dichloroethane (5 mL), stirred at 60°C until constant temperature. Dissolve methyl 3-amino-3-o-methoxyphenylacrylate (II-c) (0.1 g, 0.0005 mol) in dry 1,2-dichloroethane (10 mL) and drop it over 8 minutes Add the above solution, stir at 45°C for 1 h until the reaction is complete, add silica gel (0.12 g) to the solution and evaporate to dryness, and separate by column chromatography (ethyl acetate:petroleum ether=1:99) to obtain 0.084 g of a lavender solid, yield 60%. Melting point: 48-49°C.

[0044] 1 H-NMR (CDCl 3 , 400MHz) δ: 7.51~7.53(dd, 1H, J=1.6Hz, J=7.6Hz), 7.45~7.49(m, 1H), 7.04~7.10(t, 1H, J=7.2Hz), 7.00~7.02 (d, 1H, J=8.4Hz), 3.89(s, 3H), 3.82(s, 3H). 13 C-NMR (CDCl 3 , 100MHz) δ: 157.75(C), 157.16(C), 150.44~150.91(d, J C-F =47Hz, C), 142.66(C), 140.08(CH), 131.58(C), 1...

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 synthesis method of 2-trifluoromethyloxazole derivatives. The method is as follows: dissolving enamine compounds of which the beta-positions are not replaced in an anhydrous aprotic solvent; and oxidizing the 2-trifluoroacetyl in the presence of bis(trifluoroacetoxy)iodobenzene to further perform intramolecular condensation with amino, thus obtaining the 2-trifluoromethyloxazole derivatives. In the method, simple and available enamine compounds of which the beta-positions are not replaced are utilized as substrates, and a nontoxic and environmentally-friendly solid reagent, namely bis(trifluoroacetoxy)iodobenzene is utilized as a fluorinating agent; and the method has the advantages that the operations are simple, the conditions are mild, and the synthetized substituted 2-trifluoromethyloxazole derivatives are difficult to prepare by virtue of other methods, and the like.

Description

technical field [0001] The invention relates to a synthesis method of 2-trifluoromethyloxazole derivatives. Background technique [0002] Oxazole compounds widely exist in various natural products, and labradorins 1 represented by structural formula III is a marine natural product with anticancer activity [1] . The oxazole ring is also an important constituent unit of many drugs, for example, oxaprozin shown by structural formula IV is clinically used as an anti-inflammatory drug. In addition, some oxazole compounds are also used as antioxidants, fluorescent whitening agents, imaging agents, etc. [2] . [0003] [0004] Structural Formula III Structural Formula IV Structural Formula V [0005] Trifluoromethyl groups are present in many drug molecules. It is generally believed that the introduction of fluorine-containing functional groups to a biologically active heterocyclic molecule can change its physicochemical and biological properties, thereby potentially improv...

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): C07D263/34C07D263/32
Inventor 杜云飞赵康赵菲菲刘昕齐蕊
Owner TIANJIN 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