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

Method of asymmetric hydrogenation synthesis of chiral lactam by catalyzing 2-hydroxypyrazine compound with palladium

A hydroxypyrazine and asymmetric technology, which is applied in the field of chemical synthesis of chiral cyclic amines, can solve the problems of cumbersome steps and limited substrate range, and achieve good enantioselectivity, good air stability and high yield Effect

Active Publication Date: 2020-03-10
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although relatively good enantioselectivity can be obtained, the steps are cumbersome and the scope of substrates is limited to pyrazine-2-carboxylic acid derivatives [K.Rossen, S.A.Weissman, J.Sager, R.A.Reamer, D.Askin, R.P. Volante, P.J. Reider, Tetrahedron Lett. 1995, 36, 6419]

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 of asymmetric hydrogenation synthesis of chiral lactam by catalyzing 2-hydroxypyrazine compound with palladium
  • Method of asymmetric hydrogenation synthesis of chiral lactam by catalyzing 2-hydroxypyrazine compound with palladium
  • Method of asymmetric hydrogenation synthesis of chiral lactam by catalyzing 2-hydroxypyrazine compound with palladium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-12

[0030] Optimization of Hydrogenation Conditions of 5,6-Disubstituted-2-Hydroxypyrazine

[0031] Drop into palladium trifluoroacetate (1mol%-5mol% of substrate consumption) and chiral bisphosphine ligand (1.1mol%-5.5mol% of substrate consumption) in reaction flask, add organic solvent acetone (1.0mol%) after nitrogen displacement -4.0mL), stirred at room temperature for 30 minutes, and removed the organic solvent under reduced pressure; then, in the glove box, this catalyst was transferred to pre-placed substrate 1a (0.2mmol) and additive ( 10mol%-100mol% of the amount of substrate) in a reaction flask, moved to a reaction kettle, introduced hydrogen (400psi-1200psi), and reacted at 40-100 degrees Celsius for 24 hours; released hydrogen, and directly separated by column chromatography after removing the solvent To obtain the target product, change the types of organic solvents, additives, and chiral bisphosphine ligands in the reaction process, and obtain 12 different examples....

Embodiment 13-24

[0038] Synthesis of Chiral Lactams by Palladium-Catalyzed Asymmetric Hydrogenation of 5,6-Disubstituted-2-Hydroxypyrazines

[0039]Put palladium trifluoroacetate (3.0 mol% of the substrate amount) and (R)-TolBINAP (3.3 mol% of the substrate amount) into the reaction flask, add organic solvent acetone (1.0mL) after nitrogen replacement, and stir at room temperature for 30 minutes , and the solvent was removed under reduced pressure. Then, in the glove box, this solution was transferred to an ampoule containing substrate 1 (0.3 mmol) and p-toluenesulfonic acid monohydrate (100 mol%) with dichloromethane and benzene (1.5 mL / 1.5 mL). , moved to the reaction kettle, feed hydrogen (1000psi), and reacted for 24 hours at 80 degrees Celsius; release hydrogen, remove the solvent and separate directly to obtain pure products by column chromatography, change the type of substrate in the reaction process, and obtain 12 Different embodiments, the types of changes are shown in Table 2. The...

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 method of asymmetric hydrogenation synthesis of chiral lactam by catalyzing 2-hydroxypyrazine compound with palladium. In the formula, R is a C1-C6 alkyl group or an aryl group containing a substituent group being at least one of F, Cl, Br, CF3, Me, MeO, Et and nPr. The method employs feasible raw materials and is high in enantioselectivity of product and high in yield, wherein the enantiomeric excess can reach 90%. The catalyst is low-cost and feasible and is good in air stability, so that the method is a route with good atom economy and environment-friendly effect for the asymmetric hydrogenation synthesis of the chiral lactam from the 2-hydroxypyrazine compound. Meanwhile, the method is simple in operation, is practicable and easy, is high in yield, is environment-friendly and green, is gentle in reaction conditions, and has a potential practical application value.

Description

technical field [0001] The invention relates to a method for synthesizing chiral lactams through the asymmetric hydrogenation of 2-hydroxypyrazine compounds by highly enantioselectively catalyzing a palladium catalyst system, which belongs to the field of chemical synthesis of chiral cyclic amines. Background technique [0002] Chiral piperazinone structures widely exist in natural products and active pharmaceutical molecules. Although there are many methods to construct chiral piperazinone structures, most of these methods start from chiral amino acids and go through steps such as ring closure, so there are disadvantages such as expensive raw materials and cumbersome steps [(a) Dinsmore, C.J.; Beshore, D.C.Org.Prep.Proced.Int.2002, 34, 367; (b) Crestey, F.; Witt, M.; Jaroszewski, J.W.; Franzyk, H.J.Org.Chem.2009, 74, 5652; P.; B. Org. Lett. 2008, 10, 1473; (d) Kwon, S.H.; Lee, S.M.; Byun, S.M.; Chin, J.; S.K.; Panda, G. RSC Adv. 2013, 3, 18332;]. Using asymmetric hydro...

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): C07D241/08
CPCC07B2200/07C07D241/08
Inventor 周永贵冯广收时磊孙蕾
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