Preparation method for 7-methyl-aza-bicyclo[4,1,0]heptane

A technology of methylaminocyclohexanol and aza, applied in the direction of organic chemistry, can solve the problems of easy impurities, high-temperature ring opening of intermediates, strong corrosiveness of chlorosulfonic acid, etc., and achieve improved yield and purity, and reaction conditions Gentle, readily available ingredients

Inactive Publication Date: 2015-04-29
DALIAN NETCHEM CHIRAL TECH
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the disadvantages of this method are: (1) the first step of the reaction requires high temperature and pressure, which is difficult to control, impurities appear, and the yield is low; (2) chlorosulfonic acid in the closed-loop reaction is highly corrosive, and transportation, procurement, and storage become large Issues that affect the use of amplified compositing
[0

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
  • Preparation method for 7-methyl-aza-bicyclo[4,1,0]heptane
  • Preparation method for 7-methyl-aza-bicyclo[4,1,0]heptane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Take epoxy cyclohexane and 40% methylamine solution as starting materials, use phosphorus tribromide and triethylamine as bromination system, and use sodium hydroxide as alkali

[0026] Preparation of the first step intermediate:

[0027] Add 1kg (40%, 12.9mol, 4eq) of methylamine aqueous solution to a 2L four-necked flask equipped with magnetic stirring, thermometer, and exhaust gas absorption device, keep at 20°C, and add 316.5g (3.22mol, 1eq) epoxy ring dropwise Hexane was dripped in about 2 hours, and the reaction was continued for 15 hours. The reaction of the raw materials in the GC was completed. The water was evaporated under reduced pressure at 60 °C, and then heated to 100 °C to steam out the intermediate under reduced pressure. 395.8g (3.07mol), the yield is 95.3% , GC purity 98.3%;

[0028] Preparation of the second step product:

[0029] To a 2L four-necked flask equipped with mechanical stirring, thermometer, nitrogen protection device and cold bath, add...

Embodiment 2

[0031] Taking epoxy cyclohexane and 37% methylamine aqueous solution as starting materials, phosphorus tribromide / triethylamine system as bromination system, potassium hydroxide as alkali

[0032] Preparation of the first step intermediate:

[0033] Add 867g (37%, 10.34mol, 4eq) of methylamine aqueous solution to a 2L four-necked flask equipped with magnetic stirring, thermometer, and exhaust gas absorption device, keep at 30°C, and add 253.8g (2.59mol, 1eq) epoxy ring dropwise Hexane, dripped for about 2 hours, continued to react for 14 hours, the reaction of the raw materials controlled in the GC was completed, the water was distilled off under reduced pressure at 80 °C, and then heated to 100 °C under reduced pressure to steam out the intermediate 321.7g (2.49mol), GC purity 98.3% , the yield is 96.2%;

[0034] Preparation of the second step product:

[0035] To a 2L four-necked flask equipped with mechanical stirring, thermometer, nitrogen protection device and cold bath...

Embodiment 3

[0037] Taking epoxy cyclohexane and 35% methylamine aqueous solution as starting materials, phosphorus tribromide / triethylamine system is used as bromination system

[0038] Preparation of the first step intermediate:

[0039] Add 872g (37%, 10.44mol, 4eq) of methylamine aqueous solution to a 2L four-necked flask equipped with magnetic stirring, thermometer, and exhaust gas absorption device, keep at 25°C, and add 257.8g (2.63mol, 1eq) epoxy ring dropwise Hexane, dripped in about 2 hours, continued to react for 16 hours, the reaction of the raw materials in the GC control was completed, the water was distilled off under reduced pressure at 70 °C, and then heated to 100 °C under reduced pressure to steam out the intermediate 324.3.7g (2.51mol), the GC purity was 98.6 %, the yield is 95.5%;

[0040] Preparation of the second step product:

[0041] To a 2L four-necked flask equipped with mechanical stirring, thermometer, nitrogen protection device and cold bath, add 890g of met...

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 novel synthetic method for 7-methyl-aza-bicyclo[4,1,0]heptane. The method comprises the following two steps: firstly, reacting cyclohexene oxide with a methylamine water solution to generate an intermediate-o-methylaminocyclohexanol; secondly, generating bromide in the presence of phosphorus tribromide/triethylamine or bromine and triphenylphosphine/triethylamine, and then generating a product-7-methyl-aza-bicyclo[4,1,0]heptane. By optimizing reaction conditions and improving a path, the invention provides the novel synthetic method for 7-methyl-aza-bicyclo[4,1,0]heptanes; the intermediate in each step is easily purified and the raw materials are easily available; the method is mild in condition, simple and convenient to carry out, relatively low in cost and relatively high in yield, and can be applied to synthesis of organic amine compounds.

Description

technical field [0001] The invention relates to a preparation method of 7-methyl-aza-bicyclo[4.1.0]heptane, which belongs to the technical field of synthesis and preparation of organic chemicals. Background technique [0002] Chiral amines widely exist in nature and are the biological units of many important active molecules, and are important intermediates for the synthesis of many natural products and chiral drugs. Among them, the racemic trans-1,2-dimethylaminocyclohexane can be combined with Many metal ions (Cu 2+ , Ru 2+ , Ni) form excellent ligands for drug synthesis reactions, so more and more attention has been paid to the synthesis of trans-1,2-dimethylaminocyclohexane, and the reports of its synthetic route also appear frequently, while 7-methylaminocyclohexane -Aza-bicyclo[4.1.0]heptane is an important intermediate for the synthesis of trans-1,2-dimethylaminocyclohexane, and it is particularly important to study its analytical method. The synthetic methods repo...

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): C07D203/26
CPCC07D203/26
Inventor 安昌辉郑鹏
Owner DALIAN NETCHEM CHIRAL TECH
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