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

5-fluoro polysubstituted pyrroline derivative and preparation method thereof

A technology of dihydropyrrole and multi-substitution, applied in the direction of organic chemistry, etc., can solve the problem of less literature on the synthesis of fluorine-containing dihydropyrrole, and achieve the effects of mild reaction conditions, simple operation and easy availability of raw materials

Active Publication Date: 2016-04-13
EAST CHINA NORMAL UNIV
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there have been quite a lot of literatures reporting the synthesis strategy of dihydropyrrole, there are very few literatures on the synthesis of fluorine-containing dihydropyrrole ((a) M.S.Novikov, A.F.Khlebnikov, M.V.Shevchenko, J.Fluorine.Chem., 2003 , 123, 177; (b) M.S. Novikov, A.F. Khlebnikov, M.V. Shevchenko, R.R. Kostikov, D. Vidovic, Russ. J. Org. Chem., 2005, 41, 1496; (c) J. Ichikawa, M. Fujiwara, Y. Wada, T. Okauchi, T. Minami, Chem. Commun. 2000, 1887; (d) T. Fujita, M. Ikeda, M. Hattori, K. Sakoda, J. Ichikawa, Synthesis., 2014, 46, 1493. )

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
  • 5-fluoro polysubstituted pyrroline derivative and preparation method thereof
  • 5-fluoro polysubstituted pyrroline derivative and preparation method thereof
  • 5-fluoro polysubstituted pyrroline derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Put raw materials 3-(4-bromophenyl)-2-(trifluoromethyl)ethyl acrylate (0.45mmol), diethyl p-toluenesulfonamidomalonate (0.3mmol) into a pre-activated Molecular sieves and formula (II) in the drying reaction tube of potassium carbonate of 1.2 times of the amount of amidodiethyl malonate substance, fully react at room temperature, react for 6 hours, detect reaction by TLC and iodine cylinder color development, to the right Diethyl tosylaminomalonate disappeared completely. Add 5.0ml of distilled water after the reaction to quench the reaction, extract with diethyl ether or ethyl acetate (3*5.0ml), combine the organic phases to dry and remove the solvent by rotary evaporation, and then directly purify the crude product by silica gel flash column chromatography (petroleum ether : ethyl acetate=4:1) to obtain the pure product III-1 of 5-fluoro polysubstituted dihydropyrrole derivative (156 mg, 82%).

[0039]

[0040] Yellow oily substance. 1 HNMR (400MHz, CDCl 3 )δ8.06...

Embodiment 2

[0042] With 3-(4-bromophenyl)-2-(trifluoromethyl)ethyl acrylate (0.45mmol), diethyl acetamidomalonate (0.3mmol) as raw material, other operation reference example 1, reaction Stir for 6h, and purify by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the pure 5-fluoro polysubstituted dihydropyrrole derivative III-2 (18 mg, 12%).

[0043]

[0044] Colorless oil. 1 HNMR (500MHz, CDCl 3 )δ7.41(d,J=7.6Hz,2H),7.12(brs,2H),4.60(d,J=2.9Hz,1H),4.39-4.33(m,2H),4.21–3.96(m,1H ),3.74–3.44(m,1H),2.40(d,J=4.9Hz,3H),1.37(t,J=5.9Hz,3H),1.12(t,J=5.9Hz,3H),0.89(t ,J=6.0Hz,3H). 19 FNMR (282MHz, CDCl 3 )δ-99.39. 13 CNMR (126MHz, CDCl 3 )δ166.72(d, J=3.7Hz), 166.45, 162.74, 162.05(d, J=5.8Hz), 155.34(d, J=295.4Hz), 135.40, 135.39, 131.17, 122.24, 88.03(d, J =5.0Hz), 73.80, 63.12, 62.17, 60.51, 48.93, 23.71 (d, J = 11.2Hz), 14.02, 13.94, 13.33. HRMS (ESI) calcdforC 21 h 23 BrFNNaO 7 [M+Na + ]:522.0534,found:522.0541.

Embodiment 3

[0046] Use ethyl 3-(4-bromophenyl)-2-(trifluoromethyl)acrylate (0.45mmol), diethyl p-nitrobenzenesulfonamidomalonate (0.3mmol) as raw materials, and other operations refer to Example 1, the reaction was stirred for 4 hours, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1), and the pure 5-fluoro polysubstituted dihydropyrrole derivative III-3 (79mg, 41%) was obtained.

[0047]

[0048] Yellow oily substance. 1 HNMR (300MHz, CDCl 3 )δ8.41(s,4H),7.43(d,J=8.6Hz,2H),7.11(brs,2H),4.83(d,J=5.9Hz,1H),4.65–4.36(m,2H), 4.28–3.93(m,2H),3.91–3.60(m,2H),1.46(t,J=7.1Hz,3H),1.11(t,J=7.1Hz,3H),1.05(t,J=7.2Hz ,3H). 19 FNMR (282MHz, CDCl 3 )δ-97.31. 13 CNMR (101MHz, CDCl 3 )δ166.85,163.36,161.41(d,J=5.7Hz),155.09(d,J=295.0Hz),150.75,144.51,134.44,131.29,130.62,130.60,124.08,122.64,87.07(d,J=3.8Hz) ,77.73,63.8,63.15,60.69,50.35,13.99,13.96,13.35.HRMS(ESI)calcdforC 25 h 24 BrFN 2 NaO 10 S[M+Na + ]:665.0211,found:665.0219.

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 5-fluoro polysubstituted pyrroline derivative of the structure shown as the formula (III). According to a preparation method of the 5-fluoro polysubstituted pyrroline derivative, under the action of alkali, a trifluoromethyl-containing alkene compound and an amide diethyl malonate compound are subjected to a cyclization reaction, extraction, concentration and column chromatography to obtain the 5-fluoro polysubstituted pyrroline derivative; the reaction process is shown as the reaction formula (1). Through the preparation method, reaction conditions are mild, operation is simple, and a structural framework of a 5-fluoro polysubstituted pyrroline compound is obtained. Please see the description for the reaction formula (1).

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and relates to a preparation method of a class of fluorine-containing dihydropyrrole derivatives, in particular to a class of 5-fluoro multi-substituted dihydropyrrole derivatives and a preparation method thereof. Background technique [0002] Dihydropyrrole structural units are widely present in natural products and pharmaceutical reagents, and are often used as synthetic tetrahydropyrrole, the lead compound of pyrrole (see: (a) H.G.Cheon, H.LimandD.H.Lee, Eur.J.Pharmacol. , 2001, 411, 181; (b) H.G.Cheon, S.S.Lee, H.LimandD.H.Lee, EurJ.Pharmacol., 2001, 411, 187; (c) C.W.BirdandG.W.H.Cheeseman, inComprehensiveHeterocyclicChemistry, ed.A.R.KatritzkyandC.W.Rees , Pergamon, Oxford, UK, 1984, vol.4, p.8; (d) D.Walker and J.D.Hiebert, Chem. Rev., 1967, 67, 153; (e) Y.K.Shim, J.I.Youn, J.S.Chun, T.H. Park, M.H. Kim and W.J. Kim, Synthesis, 1990, 753.). Therefore, it is of great significance to find...

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): C07D207/48C07D207/22C07D207/24C07D207/28
CPCC07D207/22C07D207/24C07D207/28C07D207/48
Inventor 肖元晶杨洁茹周小凡曾雨黄超乾张俊良
Owner EAST CHINA NORMAL 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