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

Preparation method of phenyl (S)-N-ethyl-N-methyl-3-[1-(dimethyamino)ethyl]-amidoformate (I) and tartrate thereof (II)

A technology of phenyl carbamate and dimethylamino, applied in (S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate (I) The preparation field of its tartrate (II) can solve the problems of low total yield, waste, and high cost, and achieve the effects of simple operation, high optical purity, and convenient source of raw materials

Inactive Publication Date: 2007-03-07
SHANGHAI AOBO PHARMTECH INC LTD
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] These resolution methods mean that at least 50% of the (R)-isomer is wasted, resulting in low overall yield and high cost of the method

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 phenyl (S)-N-ethyl-N-methyl-3-[1-(dimethyamino)ethyl]-amidoformate (I) and tartrate thereof (II)
  • Preparation method of phenyl (S)-N-ethyl-N-methyl-3-[1-(dimethyamino)ethyl]-amidoformate (I) and tartrate thereof (II)
  • Preparation method of phenyl (S)-N-ethyl-N-methyl-3-[1-(dimethyamino)ethyl]-amidoformate (I) and tartrate thereof (II)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Preparation of 3-(1-(S)-(N,N-dimethylamino)ethyl)-phenyl chloroformate

[0044] Dissolve triphosgene (15.9g, 53.5mmol) in 400ml tetrahydrofuran, and add 3-(1-(S)-(N,N-dimethylamino)ethyl)-sodium phenoxide ( 25g, 133.7mmol), stirred at 0°C for 20 minutes, then heated to 55-60°C for four hours, blown off the remaining phosgene with nitrogen, filtered off sodium chloride, and concentrated to obtain an oily liquid (30g). Without purification, directly into the next reaction.

Embodiment 2

[0045] The preparation of embodiment two rivastigmine

[0046] Under ice-water bath cooling, the oily liquid (30g) obtained in Example 1 was dissolved in 200ml of anhydrous ether, and this solution was added dropwise to triethylamine (18.7mL), methylethylamine (7.9g, 133.7mmol) and 300mL of anhydrous ether mixture. Stirring was continued for 20 minutes under ice-cooling, and then reacted overnight at room temperature. Remove triethylamine hydrochloride by filtration, wash with saturated brine (2×200mL), dry over anhydrous sodium sulfate, concentrate to obtain a colorless oily liquid, distill under reduced pressure, and collect fractions at 120-122°C (about 0.5 mm Hg) , to get rivastigmine (26.8g, two-step yield 80%).

Embodiment 3

[0047] Example 3 Preparation of 3-(1-(S)-(N,N-dimethylamino)ethyl)-phenyl chloroformate

[0048] Sodium hydroxide (3.18g, 79.5mmol) was dissolved in 100mL ethanol, and slowly added dropwise to 3-(1-(S)-(N,N-dimethylamino)ethyl)-phenol hydrochloride ( 8g, 39.7mmol) in 100mL of ethanol, stirred at room temperature for 1 hour, concentrated and evaporated to dryness of ethanol and water. The resulting solid was slowly added to a solution of triphosgene (4.7 g, 15.9 mmol) in tetrahydrofuran (120 mL) cooled in an ice-salt bath, stirred at 0° C. for 20 minutes, then heated to 55-60° C. for four hours, and blown away with nitrogen. Phosgene, sodium chloride was filtered off, and concentrated to give an oily liquid (9g). Without purification, rivastigmine can be directly reacted with methylethylamine to prepare rivastigmine (operation steps refer to Example 2).

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 (S)-N-ethyl-N-methyl-3[1-(dimethylamino) ethyl]-carbamidbenzoate (I) and preparing method of tartrate (II), which comprises the following steps: reacting compound (III) or salt and phosgene, diphosgene or triphosgene to obtain compound (IV); preparing compound (I) through reacting non-purifying compound (IV) and N-methyl-N-ethyl ammonium; reacting compound (I) and L-(+)-tartaric acid to obtain tartrate (II).

Description

technical field [0001] The present invention relates to a new synthesis of (S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-carbamic acid phenyl ester (1) and its tartrate (II) method. Background technique [0002] Alzheimer's disease (abbreviated as AD) is a neurological disease caused by the death of brain nerve cells. Its symptoms are mainly the loss of memory and cognitive ability of the patient in varying degrees, and the disturbance of behavioral activities. [0003] Rivastigmine (Rivastigmine, chemical name (S)-N-ethyl-N-methyl-3-[1-(dimethylamino) ethyl]-carbamic acid phenyl ester) (I), and its tartrate ( II) has the following structural formula: [0004] [0005] Rivastigmine tartrate (II) is an effective drug used to alleviate the development of AD. Its mechanism of action is to inhibit acetylcholinesterase in the human brain and increase the content of acetylcholine in the central nervous system. It is suitable for mild to moderate patients The treatment can ...

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): C07C271/46C07C269/04
CPCC07C269/04C07C211/49C07C211/29A61P25/28C07C271/44
Inventor 马大为潘强彪潘嵩
Owner SHANGHAI AOBO PHARMTECH INC LTD
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