Preparation method of artificially synthesized (R, S)-nicotine salt

A nicotine salt, artificial synthesis technology, applied in the preparation of organic compounds, carboxylates, carboxylates and other directions, can solve the problems of many steps, increased costs, expensive reagents and the like

Inactive Publication Date: 2021-06-01
FEELLIFE BIOSCI INT
View PDF4 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Using butyllithium to exchange metals on 3-bromopyridine at low temperature also has the disadvantage of not being able to produce on a large scale
[0020] In a word, the existing methods for preparing racemic nicotine not only use expensive reagents, but also often use low-temperature reactions, many steps, long reaction cycles, increased costs, and are difficult to be used in industrial production.

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 of artificially synthesized (R, S)-nicotine salt
  • Preparation method of artificially synthesized (R, S)-nicotine salt
  • Preparation method of artificially synthesized (R, S)-nicotine salt

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051]This embodiment provides an artificial synthesis (R, S)-nicotine salt, prepared according to the following steps:

[0052]S1, Take 4-methyl amino-1- (3-pyridine)-ketone hydrochloride (13.8 g, 0.055 mol), dissolved in 160 ml of water, 5 mol / L of potassium hydroxide or hydroxide at -5 ° C The pH of the sodium adjusted reaction system is weakly alkaline to pH 8, and the stirring reaction is 5 hours;

[0053]S2, the reactant of step S1 is concentrated, the concentrate is purified and methanol mixture, and the intermediate 1-methyl-2- (3-pyridine) -2-pyrrolidanol is obtained;

[0054]S3, dissolved in an intermediate with 180 ml of water and ethanol mixture, sodium borohydride (3.8 g) was added at -5 ° C, and the mixture was stirred to 15 ° C for 2 hours;

[0055]S4, extracted with ethyl acetate, dry concentrate on crude yellow oil, add 110 ml, directly evaporated, water is extracted with 270 ml of n-hexane or tetrahydrofuran, dry concentrate 7.9g, and test the hand with high performance liqu...

Embodiment 2

[0061]This embodiment provides an artificial synthesis (R, S)-nicotine salt, prepared according to the following steps:

[0062]S1, Take 4-methyl amino-1- (3-pyridine)-ketone hydrochloride (25.1 g, 0.1 mol), dissolved in 150 ml of water and methanol, sodium carbonate or potassium carbonate at 0 ° C to 8.5 , Stirring reaction for 3 hours;

[0063]S2, concentrate the reactants of step S1, concentrate water and ethanol mixture, to obtain intermediate 1-methyl-2- (3-pyridine) -2-pyrrolidanol;

[0064]S3, the intermediate body was dissolved with 160 ml of methanol, and lithium aluminum (3.7 g, 0.1 mol) was added at 0 ° C, warmed to 25 ° C, stirred for 2 hours;

[0065]S4, with methanol extraction, dry concentrate on crude yellow oil, 210 ml of water, directly evaporated, water was extracted with 290 ml of petroleum ether or diethyl ether, dried to concentrate 12.5 g, and the rotation of rotation is zero, that is (R) , S) - nicotine. HPLC test (R, S) - nicotine has a purity of 99.5%. The oxalic acid ...

Embodiment 3

[0067]This embodiment provides an artificial synthesis (R, S)-nicotine salt, prepared according to the following steps:

[0068]S1,4-methyl amino-1- (3-pyridine)-ketone hydrochloride (25.1 g, 0.1 mol), dissolved with 165 ml of water and ethanol, 5 ° C with sodium bicarbonate or potassium hydrogencarbonate pH to 7.5 , Stir for 2 hours;

[0069]S2, concentrate the reactant of step S1, concentrate water and methanol mixture, to obtain intermediate 1-methyl-2- (3-pyridine) -2-pyrrolidanol;

[0070]S3, the intermediate body was dissolved with 180 mL of propanol or isopropyl alcohol, and potassium borohydride (5.4 g, 0.1 mol) was added at 5 ° C, and the temperature was tapered to 25 ° C, and the mixture was stirred for 2 hours;

[0071]S4, 200 ml of distilled water, evaporation, evaporated water phase, extract the evaporated water phase was extracted with ethyl acetate, and ethyl acetate was concentrated to dryness 12.0 g, and the angiographic gauge is zero, that is, (R, S) - nicotine. HPLC test (R, ...

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 preparation method of artificially synthesized (R, S)-nicotine salt. The method comprises: S1, taking 4-methylamino-1-(3-pyridine)-butanone hydrochloride and an alkaline substance, and carrying out a reaction at a temperature of -5-5 DEG C; S2, concentrating a reactant in the step S1, and adding a first refining solvent for refining, so as to obtain 1-methyl-2-(3-pyridine)-2-pyrrolidinol; S3, taking 1-methyl-2-(3-pyridine)-2-pyrrolidinol, adding a reducing agent, and carrying out a reaction at the temperature of 15-35 DEG C; and S4, concentrating the reactant in the step S3, adding a second refining solvent for refining, and then adding acid for reaction to obtain the artificially synthesized (R, S)-nicotine salt. The invention innovatively provides a two-step method for synthesizing the (R, S)-nicotine salt, and the prepared (R, S)-nicotine salt does not contain any other harmful tobacco compounds, has the advantages of simple process and high purity, and is suitable for industrial large-scale production.

Description

Technical field[0001]The present invention relates to a method of manual synthesis (R, S)-nicotine salt, specifically, from 4-methyl amino-1- (3-pyridine) -ternyl hydrochloride by two-step reaction ( R, S) - a method of nicotine salt.Background technique[0002]The information disclosed in the background is only intended to increase the understanding of the overall background of the present invention, rather than being considered as acknowledging or in any form of information, which has become known to those of ordinary skill in the art.[0003]Nicotine is also known as nicotine, is an alkaloid present in the eggplant plant, also an important component of tobacco. Nicotine is a typical agonist of nicotine acetylcholine receptors, and nicotine acetylcholine receptors have important adjustments to the central nervous system. Studies have shown that nicotine is expected to be effective drugs for treating Parkinson's disease, Alzheimer's disease, schizophrenia, epilepsy and depression. The ...

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): C07D401/04C07C59/265C07C55/07C07C53/10C07C59/245C07C59/08C07C53/126C07C59/255C07C57/32C07C51/41
CPCC07C51/412C07C53/10C07C53/126C07C55/07C07C57/32C07C59/08C07C59/245C07C59/255C07C59/265C07D401/04A61K31/465A61P25/08A61P25/18A61P25/24A61P25/28C07B55/00
Inventor 华健吕泉福
Owner FEELLIFE BIOSCI INT
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