Synthetic method of chiral 2-phenylpyrrolidine

The technology of a phenylpyrrolidine and a synthetic method is applied in the synthesis of chiral 2-phenylpyrrolidine and the synthesis field of chiral pyrrolidine, and can solve the problems of being unsuitable for industrial production, expensive reagents or catalysts, and difficult to obtain, etc., Achieve the effect of low cost, simple operation and high yield

Active Publication Date: 2015-05-06
ASTATECH CHENGDU BIOPHARM CORP
View PDF5 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] In general, the reagents or catalysts used in the current method for synthesizing chiral 2-phenylpyrrolidine are

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
  • Synthetic method of chiral 2-phenylpyrrolidine
  • Synthetic method of chiral 2-phenylpyrrolidine
  • Synthetic method of chiral 2-phenylpyrrolidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: the synthesis of (S)-2-phenylpyrrolidine:

[0041] (1) Dissolve (R)-2-amino-2-phenylacetic acid (200g, 1.32mol), potassium carbonate (218g, 1.58mol) in water (2.0L) and methanol (0.5L), cool to T <10°C, add di-tert-butyl dicarbonate (288g, 1.32mol) dropwise, react overnight at room temperature, adjust pH to 4-5 with 1N HCl, extract with ethyl acetate (1.0L*3), and saturated saline (1.0 L*1) was washed and concentrated to obtain 315 g of white solid with a yield of 95%.

[0042] h 1 NMR (400MHz, DMSO-d6): 12.74(s, 1H), 7.55(d, J=8Hz, 1H), 7.38-7.3(m, 5H), 5.10(d, J=8Hz, 1H), 1.39(s ,9H).

[0043] (2) Add (R)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (300g, 1.19mol), 4-dimethylaminopyridine (260g, 2.12mol), cycloisopropylidene malonate The ester (205g, 1.43mol) was dissolved in dichloromethane (3.0L), and N,N-dicyclohexylcarbodiimide (370g, 1.79mol) was dissolved in dichloromethane (0.5L), keeping the temperature at Drop into the reaction system ...

Embodiment 2

[0049] Embodiment 2: the synthesis of (R)-2-phenylpyrrolidine:

[0050] (1) Dissolve (S)-2-amino-2-phenylacetic acid (100g, 0.66mol), potassium carbonate (109g, 0.79mol) in water (1.0L) and methanol (0.25L), cool to T <10°C, add di-tert-butyl dicarbonate (144g, 0.66mol) dropwise, react overnight at room temperature, adjust pH to 4-5 with 1N HCl, extract with ethyl acetate (0.5L*3), and saturated saline (0.5 L*1) was washed and concentrated to obtain 150 g of white solid with a yield of 90%.

[0051] h 1 NMR (400MHz, DMSO-d6): 12.72(s, 1H), 7.53(d, J=8Hz, 1H), 7.38-7.3(m, 5H), 5.09(d, J=8Hz, 1H), 1.38(s ,9H).

[0052] (2) (S)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (150g, 0.59mol), 4-dimethylaminopyridine (130g, 1.06mol), cycloisopropylidene malonate Ester (102g, 0.71mol) was dissolved in dichloromethane (1.5L), and N,N-dicyclohexylcarbodiimide (185g, 0.89mol) was dissolved in dichloromethane (0.25L), keeping the temperature at Drop into the reaction system at 0-1...

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 synthetic method of chiral 2-phenylpyrrolidine. The synthetic method comprises the following steps: (1) butoxycarbonyl protective reaction: carrying out reaction on chiral 2-amino-phenylacetic acid and di-tert-butyl dicarbonate to obtain chiral 2-( butoxycarbonyl amino)-2-phenylacetic acid; (2) condensation and reduction reaction: carrying out condensation on the chiral 2-(butoxycarbonyl amino)-2-phenylacetic acid and 2, 2-dimethyl-1, 3-dioxane-4, 6-dione, and carrying out reduction by virtue of sodium borohydride to obtain chiral 2-(2, 2-dimethyl-4, 6-dicarbonyl-1, 3-dioxane-5-yl)-1-phenyl ethyl tert-butyl carbamate; (3) de-protection and heating ring closure reaction: carrying out de-protection and heating ring closure reaction on the chiral 2-(2, 2-dimethyl-4, 6-dicarbonyl-1, 3-dioxane-5-yl)-1-phenyl ethyl tert-butyl carbamate to obtain chiral 5-phenylpyrrolidine-2-ketone; and (4) reduction reaction: reducing the chiral 5-phenylpyrrolidine-2-ketone by virtue of lithium aluminium hydride to obtain the chiral 2-phenylpyrrolidine. The synthetic method is simple in operation, high in yield and cheap and easily acquired in raw materials and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and relates to a synthesis method of chiral pyrrolidine, in particular to a synthesis method of chiral 2-phenylpyrrolidine. Background technique [0002] Tetrahydropyrrole derivatives are the components or chemical intermediates of many medicines, and are also widely used in the fields of food, medicine, pesticides, coatings, printing and dyeing, papermaking, textiles, photosensitive materials, daily chemicals, and polymer materials. From the perspective of the pharmaceutical industry alone, many compounds containing tetrahydropyrrole fragments have been found to have antifungal, antitumor, antipsychotic, analgesic, antileprosy, and therapeutic activities for cardiovascular and cerebrovascular diseases. Therefore, the research on the synthesis and biological activity of these compounds has attracted more and more attention. [0003] At present, there have been many reports on the synthesis of ch...

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): C07D295/023C07D295/027
CPCY02P20/582C07D207/06
Inventor 魏庚辉宁兆伦庄述坚黄显郭鹏
Owner ASTATECH CHENGDU BIOPHARM CORP
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
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap