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

Novel method for synthesizing chiral beta-aryl-gamma-aminobutyric acid compounds

A technology of aminobutyric acid and a synthesis method, which is applied in the preparation of organic compounds, chemical instruments and methods, organic chemistry and other directions, can solve the problems of unobtainable starting materials, high preparation cost, complicated synthesis route and the like, and achieves reduction of synthesis cost. , the reaction conditions are mild and controllable, and the effect of shortening the reaction steps

Inactive Publication Date: 2008-12-31
EAST CHINA UNIV OF SCI & TECH +1
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods either have cumbersome synthetic routes or are not easy to obtain starting materials, resulting in high preparation costs and are not suitable for large-scale industrial production.

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
  • Novel method for synthesizing chiral beta-aryl-gamma-aminobutyric acid compounds
  • Novel method for synthesizing chiral beta-aryl-gamma-aminobutyric acid compounds
  • Novel method for synthesizing chiral beta-aryl-gamma-aminobutyric acid compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (R)-3-(4-Chlorophenyl)-4-nitro-butyraldehyde (IIa)

[0029]

[0030] In 2 ml In ethanol, stirred and reacted at 0°C for 15 hours, the crude product was separated by column chromatography (eluent: ethyl acetate:petroleum ether=1:4) to obtain (R)-3-(4-chlorophenyl)- 4-nitrobutyraldehyde (IIa), yield (73%), 1 H NMR (500MHz, CDCl 3 ): 9.70(s, 1H), 7.32(d, 2H; J=8.5Hz), 7.18(d, 2H; J=8.0Hz), 4.57-4.69(m, 2H), 4.05-4.07(m, 1H) , 2.94 (d, 2H; J=6.5Hz); HPLC (Chiralpak AS-H, iPrOH / hexanes=30 / 70, flow rate=0.5mL / min, λ=210nm): t major =40.09min,t minor =32.08min, ee=96%; [α] D 25 =+11.5 (c=1.0in CHCl 3 ).

Embodiment 2

[0032] (S)-3-(4-Chlorophenyl)-4-nitro-butyraldehyde (IIIa)

[0033]

[0034] Replace (R)-diphenylpyrrolidine trimethylsilyl ether with (S)-diphenylpyrrolidine trimethylsilyl ether, and the rest of the required raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S) -3-(4-chlorophenyl)-4-nitrobutyraldehyde (IIIa), yield (75%), 1 H NMR (500MHz, CDCl 3 ): 9.71(s, 1H), 7.32(d, 2H; J=8.5Hz), 7.18(d, 2H; J=8.0Hz), 4.57-4.69(m, 2H), 4.05-4.08(m, 1H) , 2.94(d, 2H; J=7.0Hz); 13 C NMR (125MHz, CDCl 3 ): δ198.2, 136.7, 129.4, 128.8, 79.1, 46.3, 37.3; HPLC (Chiralpak AS-H, i-PrOH / hexanes=30 / 70, flow rate=0.5mL / min, λ=210nm): t major =31.64min,t minor =43.79min, ee=97%; [α] D 25 =-11.7 (c=1.0 in CHCl 3 ).

Embodiment 3

[0036] (S)-3-(4-nitrophenyl)-4-nitro-butanal (IIIb)

[0037]

[0038] Replace (E)-3-(4-chlorophenyl)acrolein with (E)-3-(4-nitrophenyl)acrolein, and the rest of the required raw materials, reagents and preparation methods are the same as in Example 2 to obtain (S)-3-(4-nitrophenyl)-4-nitrobutanal (IIIb), yield 72%. 1 H NMR (500MHz, CDCl 3 ): 9.74(s, 1H), 8.22(d, 2H; J=8.5Hz), 7.45(d, 2H; J=8.5Hz), 4.65-4.79(m, 2H), 4.21-4.23(m, 1H) , 3.04(d, 2H; J=7.0Hz); 13 C NMR (125MHz, CDCl 3 ): δ197.5, 147.6, 145.7, 128.6, 124.3, 78.4, 46.1, 37.5; [α] D 25 =+7.2 (c=1.0in CHCl 3 ).ee=99%.

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 and simple synthetic methodsynthesis method for chiral beta-aryl-gamma-aminobutyric acid compounds as shown in structural formula I. The method takes chiral diphenyl pyrrolidine trimethylsilyl ether as a catalyst and takes the cheap nitromethane and 3-aryl-acrolein as raw materials; the catalyst and the raw materials are reacted in alcohol solvent for 5 to 40 hours to prepare the chiral beta-aryl-gamma-nitryl-butyraldehyde with high yield (65-82%) and high counterpart selectivity (96-99%); then the chiral beta-aryl-gamma-nitryl-butyraldehyde is taken as the key intermediate to go through aldehyde oxidation and nitro reduction to get the chiral beta-aryl-gamma-aminobutyric acid (baclofen compounds). Compared with the existing synthetic route for baclofen compounds, the reaction steps of the invention are significantly shortened from the usual 6-8 steps to 3 steps, and the reaction conditions are mild and controllable, thereby greatly reducing the synthetic costs of baclofen drugs.

Description

technical field [0001] The invention belongs to the field of selective catalytic synthesis of counterparts, and more specifically relates to a novel and simple synthesis method of chiral β-aryl-γ-aminobutyric acid compounds (baclofen derivatives) with structural formula I. Background technique [0002] Baclofen (baclofen) is a derivative of γ-aminobutyric acid (GABA), a skeletal muscle relaxant and sedative that acts on the brain and spinal cord of the central nervous system. It is generally believed that the content of GABA in the brain and spinal cord of the human central nervous system is very high, which is more than 1000 times higher than that of monoamines in the brain such as catecholamines, norepinephrine, and dopamine. Among them, the content in the substantia nigra and globus pallidus The highest, about 20 to 40% of the synapses in the brain use GABA as a transmitter. GABA is the main inhibitory transmitter in the central nervous system brain and spinal cord, but ...

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): C07C205/53C07C201/12
Inventor 王卫蒋华良
Owner EAST CHINA UNIV OF SCI & TECH
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