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

Method for asymmetric hydrogenation of isoquinoline by activation of halogen bond

An isoquinoline and asymmetric technology is applied in the field of catalytic hydrogenation of fluorine-containing pyridine to synthesize chiral fluorine-containing piperidine derivatives, and achieves the effects of convenient preparation, high reactivity and enantioselectivity, and realizing chirality value-added.

Inactive Publication Date: 2019-03-05
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 2006, Zhou's group used the strategy of chloroformate to activate the substrate for the first time to realize the asymmetric hydrogenation of 1-substituted isoquinoline derivatives, but only moderate enantioselectivity and yield were obtained, and deesterification was required base protection

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
  • Method for asymmetric hydrogenation of isoquinoline by activation of halogen bond
  • Method for asymmetric hydrogenation of isoquinoline by activation of halogen bond
  • Method for asymmetric hydrogenation of isoquinoline by activation of halogen bond

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: optimization of conditions

[0032] In a nitrogen-filled glove box, add (1,5-cyclooctadiene) iridium chloride dimer (0.0025 mmol, 1.7 mg) and chiral ligand (0.0055 mmol) to a reaction vial Add 1 ml of tetrahydrofuran, stir at room temperature for 10-30 minutes, then add halide and stir for 10-30 minutes, add isoquinoline (0.25 mmol) to the reaction flask with catalyst, and then add 2 ml of tetrahydrofuran. Put the reaction bottle into a stainless steel autoclave, feed hydrogen gas at 1200psi, and react at 80 degrees for 20-48 hours. Slowly release hydrogen, and add saturated Na to the system 2 CO 3 The aqueous solution was stirred for 10 minutes, then extracted three times with dichloromethane, the organic phases were combined and dried, and the solvent was removed by a rotary evaporator after direct column chromatography (the volume ratio of eluent sherwood oil and ethyl acetate was 10:1-5: 1) Isolate and obtain pure product, reaction formula and ligan...

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

Disclosed is a method for asymmetric hydrogenation of isoquinoline by activation of a halogen bond. A catalytic system used by the method is a chiral diphosphine complex of iridium, and an activator is halides. An reaction can be carried out under the following conditions: the temperature is 25-100 DEG C, a solvent is tetrahydrofuran, the pressure is 13-100 atmospheres, a ratio of a substrate to acatalyst is 50 / 1, and the catalyst is a complex of (1,5-cyclooctadiene) iridium chloride dimer and a bisphosphine ligand. The isoquinoline is hydrogenated to obtain corresponding chiral tetrahydroisoquinoline derivatives, and an enantiometric excess can reach 99%. The method has the advantages of simple and practical operation, easy availability of raw materials, high enantioselectivity and goodyield, and the reaction has the advantages of green atom economy, environmental friendliness and the like.

Description

technical field [0001] The invention relates to a method for synthesizing chiral fluoropiperidine derivatives by using iridium homogeneous system to catalyze the hydrogenation of fluoropyridine with high enantioselectivity. technical background [0002] Chiral 1,2,3,4-tetrahydroisoquinolines are a class of extremely important alkaloid intermediates, which widely exist in natural products and pharmaceutical chemicals, and have a broad spectrum of physiological and pharmacological activities, such as: anti Viral, sedative, relieve muscle tension, antihypertensive and hallucinogenic effects, etc. Therefore, the research on the synthesis and biological activity of this kind of compounds has aroused extensive attention of organic chemists and pharmaceutical circles. The following formula 1 just has pharmaceutical activity to contain the structural unit of chiral tetrahydroisoquinoline: [0003] [0004] Given the importance of chiral tetrahydroisoquinolines and their derivat...

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): C07D217/02C07D217/14C07D217/16C07D217/22B01J31/24
CPCB01J31/2409B01J2231/646B01J2531/827C07B2200/07C07D217/02C07D217/14C07D217/16C07D217/22
Inventor 周永贵陈木旺姬悦王杰高翔孙蕾
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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