Preparation method of N-t-butyloxycarbonyl piperazine

A technology of tert-butoxycarbonylpiperazine and solvent medium, which is applied in the field of synthesis of pharmaceutical intermediates, and can solve problems such as high price, low product yield, and difficult preparation

Active Publication Date: 2021-07-30
UNIV OF JINAN
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] This process is a new synthetic method, but also has the following problems: (1) this process is the same as piperazine and Boc 2 There is no essential difference in the direct reaction of O, and there is also a problem of selectivity. N - tert-butoxycarbonylpiperazine can still continue to react with tert-butyl phenyl carbonate
(2) Using tert-butyl phenyl carbonate as a raw material, the price is high and the preparation is difficult, which makes the production cost of this process relatively high, which is not conducive to industrial production
This process uses piperazine and Boc 2 O molar ratio is 1:1 to react, has reduced the consumption of piperazine, and reaction process is simple, is easy to realize suitability for industrialized production, but this technology also has many problems as follows: (1) used glacial acetic a

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 N-t-butyloxycarbonyl piperazine
  • Preparation method of N-t-butyloxycarbonyl piperazine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Add ethylenediamine (18.1 g, 1.1 eq) to a 500 mL three-necked flask, add 50 mL of methanol, start stirring, cool the reaction system below 10°C, add 40% chloroacetaldehyde aqueous solution (53.6 g, 1 eq) dropwise, drop The addition time is about 1 hour, after the addition is completed, the temperature is raised to 20-30°C, and the reaction is carried out for 2 hours. After reaction at ℃ for 3 hours, dichloromethane (50 mL + 20 mL) was added to extract twice after the reaction was completed, the organic phases were combined and concentrated to obtain 19.6 g of compound I with a yield of 85.4% and a purity of 97.7% by gas chromatography;

[0025] Compound I (50 g, 1 eq) was added to a 500 mL three-neck flask, 250 mL of methanol was added, and BocO 2 Acid anhydride (142.9 g, 1.1 eq), the dropwise addition time is about 1 hour, after the dropwise addition is completed, react at 25°C for 2 hours, the TLC control reaction is completed, add sodium borohydride (11.3 g, 0.5 eq) ...

Embodiment 2

[0027] Add ethylenediamine (20 g, 1 eq) to a 500 mL three-necked flask, add 50 mL of methanol, start stirring, cool the reaction system to below 10°C, add 40% aqueous solution of chloroacetaldehyde (65.3 g, 1 eq) dropwise, The dropping time is about 1 hour. After the dropping is completed, the temperature is raised to 20-30°C, and the reaction is performed for 2 hours. At a temperature of 20-30°C, 60 g of aqueous sodium hydroxide solution (w=30%) is added dropwise. React at 45°C for 3 hours. After the reaction is completed, dichloromethane (50 mL + 20 mL) is added to extract twice, and the organic phases are combined and concentrated to obtain 20.6 g of compound I with a yield of 73.7% and a purity of 97.2% by gas chromatography;

[0028] Compound I (50 g, 1 eq) was added to a 500 mL three-neck flask, 250 mL of methanol was added, and BocO 2 Acid anhydride (129.9 g, 1 eq), the dropwise addition time is about 1 hour, after the dropwise addition is completed, react at 25°C for 2...

Embodiment 3

[0030] Add ethylenediamine (20 g, 1.1 eq) to a 500 mL three-necked flask, add 50 mL of methanol, start stirring, cool the reaction system to below 10 °C, add dropwise 40% chloroacetaldehyde aqueous solution (59.4 g, 1 eq), The dropping time is about 1 hour. After the dropping is completed, the temperature is raised to 20-30°C, and the reaction is carried out for 2 hours. At 20-30°C, 60 g of aqueous sodium hydroxide solution (w=30%) is added dropwise. React at 30°C for 3 hours. After the reaction is completed, dichloromethane (50 mL + 20 mL) is added to extract twice, and the organic phases are combined and concentrated to obtain 18.8 g of compound I with a yield of 67.4% and a purity of 97.6% by gas chromatography;

[0031] Add compound I (30 g, 1 eq) into a 500 mL three-neck flask, add 250 mL of methanol, and add BocO 2 Acid anhydride (85.7 g, 1.1 eq), the dropwise addition time is about 1 hour, after the dropwise addition is completed, react at 35°C for 2 hours, the reaction...

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 N-t-butyloxycarbonyl piperazine, and belongs to the field of synthesis of drug intermediates. According to the method, ethylenediamine is taken as a raw material, and the N-t-butyloxycarbonyl piperazine is prepared through ring closing, acylation reaction and reduction reaction. The invention provides the preparation method of the N-t-butyloxycarbonyl piperazine. The method is simple and convenient to operate, high in atom utilization rate and good in product purity.

Description

technical field [0001] The invention belongs to the field of synthesis of pharmaceutical intermediates and relates to a N - A process for the preparation of tert-butoxycarbonylpiperazine. Background technique [0002] Piperazine and its derivatives are used in medicine, surfactants, pesticides and other fields due to their special structures. Piperazine salts have anticholinergic effects, and are often used clinically as roundworm and pinworm drugs. Compared with other types of antitumor drugs, piperazine antineoplastic drugs have the advantages of broad antitumor spectrum and low toxicity. Compounds containing N-substituted piperazine can show a wide range of biological activities, such as antimicrobial, anticancer, antihypertensive, sedative and hypnotic, etc., so N-derivatives of piperazine are widely used in the pharmaceutical industry, N-Boc -Piperazine is an important basic chemical raw material for many antitussives, antiallergics, antipsychotics, antibacterials, an...

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): C07D295/205
CPCC07D295/205Y02P20/55
Inventor 刘峰旭张启龙郑庚修高令峰高禄丰
Owner UNIV OF JINAN
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