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

Synthetic method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol

A synthetic method, the technology of chroman, applied in the field of preparation of 2-amino-1-ethanol compounds, can solve the problems of many reaction steps, harsh reaction conditions, low yield, etc., achieve mild conditions, easy operation, and synthetic route short effect

Active Publication Date: 2016-04-20
BEIJING NORMAL UNIVERSITY +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to overcome the problems of many reaction steps, complex reaction operation, harsh reaction conditions and low yield in the existing literature reports, and provide a synthetic method with mild conditions, simple and convenient operation, short synthetic route, and suitable for batch production. Route of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol

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 2-amino-1-(-6-fluoro-2-chromanyl)ethanol
  • Synthetic method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol
  • Synthetic method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 6-Fluorochroman-2-carboxylic acid (1 g) was dissolved in THF (10 mL), carbonyldiimidazole (1 g) was added with stirring at room temperature, and the mixture was heated to reflux for 1 to 5 hours to obtain an acyl imidazole solution. Potassium tert-butoxide (1 g) and THF (15 mL) were mixed, and nitromethane (2 mL) was added dropwise with stirring at room temperature, and stirred at room temperature for 1 to 5 hours. Mix the acyl imidazole solution and nitromethane solution, heat and reflux for 3 to 20 hours, cool, add water (50mL), adjust the pH value to acidic with hydrochloric acid, add ethyl acetate (50mL) for extraction, wash the organic phase with water, dry, spin The solvent was distilled off to obtain a crude product, which was recrystallized from ethanol to obtain a white solid (III) (0.92 g, yield 75%), melting point 69-71 °C,1 HNMR (400MHz, CDCl 3 )δ2.08-2.13(m,1H),2.33-2.35(m,1H),2.80-2.89(m,2H),4.69(dd,J=9.5,3.2Hz,1H),5.52(d,J= 16.0Hz, 1H), 5.68(d, J=16.0Hz,...

Embodiment 2

[0053] Mix 6-fluorochroman-2-carboxylic acid (1g) with toluene (10mL), add thionyl chloride (1mL), install a gas absorption device, and heat to reflux for 1 to 5 hours. Remove the solvent and unreacted thionyl chloride under reduced pressure, add dichloromethane (10 mL), add imidazole (0.7 g), and stir at room temperature for 1 to 5 hours. Potassium tert-butoxide (1 g) and THF (15 mL) were mixed, and nitromethane (2 mL) was added dropwise with stirring at room temperature, and stirred at room temperature for 1 to 5 hours. Mix the acyl imidazole solution and nitromethane solution, heat and reflux for 3 to 20 hours, cool, add water (50mL), adjust the pH value to acidic with hydrochloric acid, add ethyl acetate (50mL) for extraction, wash the organic phase with water, dry, spin The solvent was distilled off to obtain a crude product, which was recrystallized from ethanol to obtain a white solid (III) (0.98g, yield 80%), melting point 69-71°C, 1 HNMR (400MHz, CDCl 3 )δ2.08-2.13(...

Embodiment 3

[0055] Dissolve the product (III) (0.92g) obtained in Example 1 in THF (20mL), drop it into a mixture of lithium aluminum hydride (0.4g) and THF (20mL) cooled in an ice-water bath, and continue stirring for 1~ 5 hours. Slowly add water to terminate the reaction, extract three times with dichloromethane, dry the extract, and rotary evaporate to obtain the product 2-amino-1-(-6-fluoro-2-chromanyl)ethanol (IV) (0.51g, yield 63 %). 1 HNMR (400MHz, CDCl 3 )δ1.87-1.99 (m, 4H), 2.73-3.00 (m, 4H), 3.63-3.67 (m, 1H), 3.94-3.98 (m, 1H), 6.73-6.79 (m, 3H).

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 synthesis method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol, which comprises the following steps: synthesizing 6-fluorochromanyl-2-carboxylic acid (I) used as an initial raw material into 6-fluorochromanyl-2-formacylimidazole (II); synthesizing the obtained 6-fluorochromanyl-2-formacylimidazole (II) into 1-(6-fluoro-2-chromanyl)-2-nitro-1-ethyl ketone (III); and finally, reducing the obtained 1-(6-fluoro-2-chromanyl)-2-nitro-1-ethyl ketone (III) into 2-amino-1-(-6-fluoro-2-chromanyl)ethanol (IV). The method provided by the invention has the advantages of accessible raw materials and mild reaction conditions, and is simple to operate and more suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry and relates to a preparation method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol compounds. Background technique [0002] There are two chiral centers in the 2-amino-1-(-6-fluoro-2-chromanyl)ethanol molecule, which can have four optical isomers, wherein (R)-2-amino-1-(( S)-6-fluoro-2-chromanyl)ethanol and (R)-2-amino-1-((R)-6-fluoro-2-chromanyl)ethanol are synthetic cardiovascular drugs nebivolol important intermediates. Their synthetic methods have been reported in the literature, among which Tetrahedron (2000,56,6339) and Organic Chemistry (2008,28,511) reported that p-fluorophenol was used as a raw material to synthesize allyl alcohol compounds through multi-step reactions, and then through cyclization Oxidation reaction, tosylation reaction, azidation reaction and reduction reaction give the product aminoalcohol. [0003] [0004] Literature Synthesis (2007, (8), 1154-1158) reported that ...

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 Patents(China)
IPC IPC(8): C07D311/04
CPCC07D311/58
Inventor 张站斌杨维芳王学斌唐志刚张俊波
Owner BEIJING NORMAL UNIVERSITY
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