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

Method for preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride

A technology of diethyl acetamidomalonate and alkylphenyl, applied in the preparation of 2-amino-2-[2-(4-alkylphenyl)ethyl]-1,3-propanediol hydrochloride field, can solve the problems of long reaction steps and labor protection, and achieve the effects of mild reaction conditions, short production cycle and high yield

Active Publication Date: 2012-11-28
NANJING HUAWE MEDICINE TECH DEV +1
View PDF5 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction steps are long, and a large amount of carcinogenic formaldehyde is used in the carboxymethylation process, and there are labor protection problems

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 preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride
  • Method for preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride
  • Method for preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1, Preparation of 2-acetylamino-2-[2-(4-octylphenyl)-2-oxoethyl]diethyl malonate (Ⅲ)

[0033] Under nitrogen protection, dissolve 0.2kg of 2-chloro-1-(4-octylphenyl)ethanone, 0.2kg of diethyl acetamidomalonate, 0.21kg of potassium carbonate and 2.5g of potassium iodide in 2L of 4-methyl -2-Pentanone, react at 100°C.

[0034] After 24 hours of reaction, TLC detection (petroleum ether: ethyl acetate = 3:2), 2-chloro-1-(4-octylphenyl)ethanone disappeared, stop heating, cool the reaction solution to room temperature, and pour it into 2L of water , stirred, separated, the aqueous layer was extracted with 0.5L 4-methyl-2-pentanone, the organic layers were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the filtrate was concentrated to dryness under reduced pressure to obtain 0.3kg of reddish-brown oily substance, namely intermediate III diethyl 2-acetamido-2-[2-(4-octylphenyl)-2-oxoe...

Embodiment 2

[0036] Example 2, Preparation of 2-acetylamino-2-[2-(4-octylphenyl)-2-oxoethyl]diethyl malonate (Ⅲ)

[0037] Under nitrogen protection, dissolve 2kg 2-chloro-1-(4-octylphenyl)ethanone, 1.95kg diethyl acetamidomalonate, 2.07kg potassium carbonate and 25g potassium iodide in 20L 4-methyl-2 - Pentanone, react at 100°C.

[0038] After 25 hours of reaction, TLC detection (petroleum ether: ethyl acetate = 3:2), 2-chloro-1-(4-octylphenyl)ethanone disappeared, stop heating, cool the reaction solution to room temperature, and pour it into 20L of water , stirred, separated, the aqueous layer was extracted with 5L 4-methyl-2-pentanone, the organic layers were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the filtrate was concentrated to dryness under reduced pressure to obtain red 3.22kg of brown oil, that is, diethyl 2-acetamido-2-[2-(4-octylphenyl)-2-oxoethyl]malonate (Ⅲ), yield: >95%. Mass spectru...

Embodiment 3

[0039] Example 3, Preparation of 2-acetylamino-2-[2-(4-octylphenyl)-2-oxoethyl]diethyl malonate (Ⅲ)

[0040] Under nitrogen protection, dissolve 0.4kg of 2-bromo-1-(4-octylphenyl)ethanone, 0.39kg of diethyl acetamidomalonate, 0.42kg of potassium carbonate and 10g of potassium iodide in 4L of 2-methyltetrahydrofuran, Reflux reaction at 86°C.

[0041] After 20 hours of reaction, TLC detection (petroleum ether: ethyl acetate = 3:2), 2-bromo-1-(4-octylphenyl)ethanone disappeared, stop heating, cool the reaction solution to room temperature, and pour it into 4L of water , stirred, separated, the aqueous layer was extracted with 1L 2-methyltetrahydrofuran, the organic layers were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the filtrate was concentrated to dryness under reduced pressure to obtain 0.52 kg of reddish-brown oil , that is, 2-acetylamino-2-[2-(4-octylphenyl)-2-oxoethyl]diethyl malona...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a method for preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride. The method comprises the following steps of: firstly, enabling a compound shown as a formula (II) and diethyl acetamidomalonate to be subjected to a condensation reaction under the action of a catalyst to obtain a compound shown as a formula (III); enabling the compound shown as the formula (III) as well as triethyl silane and titanium tetrachloride to be subjected to a reaction to prepare a compound (IV); then, continuously enabling the compound (IV) as well as lithium aluminum hydride and acetic anhydride to be subjected to a reaction to prepare a compound (V); and finally, enabling the compound (V) as well as lithium hydroxide and concentrated hydrochloric acid to be subjected to a reaction to obtain a compound shown as the formula (I). A midbody (III) prepared by using the method provided by the invention has enough purity and high yield up to over 95%, and purification through column chromatography is not needed in the reaction process, so that the next reaction can be directly carried out. The final target compound is synthesized by using easily purchased raw materials in a short way, and the method is short in production period, high in yield, mild in reaction condition, simple and feasible and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride and its intermediate. Background technique [0002] 2-Amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride (fingolimod, referred to as FTY-720), is a new type of immunosuppressant, available For the treatment of multiple sclerosis, it is the first sphingosine 1-phosphate receptor modulator that prevents the exit of lymphocytes from lymph nodes. It keeps specific immune cells in the lymph nodes, preventing them from acting on the central nervous system and causing damage. Pharmacological experimental studies have proved that the compound can prolong the survival period of animals in rat skin transplantation, heart transplantation and dog kidney transplantation experiments. Moreover, the toxicity of the compound is significantly lower than that of clinically used immunosuppressants, and it will have a good prospect. It is of great...

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): C07C233/47C07C231/12C07C215/28C07C213/08
Inventor 张孝清包金远徐峰蒋玉伟
Owner NANJING HUAWE MEDICINE TECH DEV
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