Method for synthesizing 2-(7-(benzyloxy)benzo[d][1, 3]dioxazole-5-yl)ethylamine and hydrochloride thereof

A synthetic method, bisoxazole technology, applied in the field of drug synthesis, can solve the problems of difficult to buy reagents, long routes, dangerous operation, etc., and achieve the effect of improving conversion rate and reducing cost

Inactive Publication Date: 2012-09-26
南京正济医药销售有限公司 +1
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] This method uses highly toxic cyanide, which has disadvantages such as long route, dangerous operation, and controlled reagents are difficult to buy.

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 synthesizing 2-(7-(benzyloxy)benzo[d][1, 3]dioxazole-5-yl)ethylamine and hydrochloride thereof
  • Method for synthesizing 2-(7-(benzyloxy)benzo[d][1, 3]dioxazole-5-yl)ethylamine and hydrochloride thereof
  • Method for synthesizing 2-(7-(benzyloxy)benzo[d][1, 3]dioxazole-5-yl)ethylamine and hydrochloride thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] The first step: preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3)

[0015]

[0016] Add 50g of 7-methoxybenzo[d][1,3]dioxazole-5-carbaldehyde (1), 76.6g of formic acid, 84g of triethylamine, malonic acid cyclo(sub) Isopropyl ester (2) 48g, the reaction solution was stirred and heated at 110 degrees to react, and the reaction was stopped after TLC detection. Cool the reaction solution to room temperature, slowly pour it into 1L of ice water, stir from side to side, adjust the pH to 2-3 with concentrated hydrochloric acid, filter the precipitated solid, stir the filter cake with water twice, and dry it in vacuum to obtain 59.4 g of the product, with a yield of 95.6 %.

[0017] The second step: the preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)ethylamine (4)

[0018]

[0019] Add 50 g of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3), 178 mL of toluene, 13.5 g of triethylamine, and 36.8g of diphenyl phosphate nitrogen, hea...

Embodiment 2

[0024] The first step: preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3)

[0025]

[0026] Add 50g of 7-methoxybenzo[d][1,3]dioxazole-5-carbaldehyde (1), 76.6g of formic acid, 84g of triethylamine, malonic acid cyclo(sub) Isopropyl ester (2) 60g, the reaction solution was stirred and heated at 100°C for reaction, and the reaction was stopped after TLC detection. Cool the reaction solution to room temperature, slowly pour it into 1L of ice water, stir from side to side, adjust the pH to 2-3 with concentrated hydrochloric acid, filter the precipitated solid, stir the filter cake with water twice, and dry it in vacuum to obtain 51.8 g of the product, with a yield of 83.5 %

[0027] The second step: the preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)ethylamine (4)

[0028]

[0029] Add 50 g of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3), 178 mL of toluene, 1.8 g of triethylamine, and Diphenyl phosphate nitrogen was 29.4g, and af...

Embodiment 3

[0034] The first step: preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3)

[0035]

[0036] Add 50g of 7-methoxybenzo[d][1,3]dioxazole-5-carbaldehyde (1), 38.3g of formic acid, 84g of triethylamine, malonate cyclo(sub) Isopropyl ester (2) 60g, the reaction solution was stirred and heated at 80 degrees to react, and the reaction was stopped after TLC detection. The reaction solution was cooled to room temperature, slowly poured into 1L of ice water, stirred side by side, adjusted to pH 2-3 with concentrated hydrochloric acid, precipitated solid was filtered, the filter cake was stirred twice with water, and vacuum dried to obtain 40.9 g of the product with a yield of 66 %.

[0037] The second step: the preparation of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)ethylamine (4)

[0038]

[0039] Add 50 g of 3-(7-methoxybenzo[d][1,3]dioxazol-5-yl)propionic acid (3), 178 mL of toluene, 18.0 g of triethylamine, and 49.0g of diphenyl phosphate nitrogen, heate...

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 method for synthesizing 2-(7-(benzyloxy)benzo[d][1, 3]dioxazole-5-yl)ethylamine and a hydrochloride thereof. In the method, 7-methoxyl benzo[d][1, 3]dioxazole-5-formaldehyde is taken as the raw material, 3-(7-methoxyl benzo[d][1, 3]dioxazole-5-yl)propionic acid is synthesized by using a one-step method of reductive condensation and hydrolysis-decarboxylation, and a Curtius rearrangement is carried out to generate 3-(7-methoxyl benzo[d][1, 3]dioxazole-5-yl)ethylamine hydrochloride(5). The method has advantages of mild reaction conditions, simple operation, low cost and high yield.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, in particular to the key intermediate 2-(7-(benzyloxy)benzo[d][1,3]dioxazol-5-yl)ethylamine and The synthetic method of its hydrochloride. technical background [0002] Narcotine is a natural isoquinoline alkaloid extracted from poppy plant opium, which has been used as an oral antitussive for more than 100 years. In recent years, narcotin has shown good anticancer effects in some animal models. Narcotine has been obtained through plant extraction for a long time, and opium poppy, as the only plant source of narcotine, has been strictly regulated. In the artificial synthesis of noscapine, 2-(7-methoxybenzo[d][1,3]dioxazol-5-yl)ethylamine hydrochloride is used as a key intermediate, and there are not many synthetic methods. CN101775021 discloses the synthetic method of brominated analogue, generates benzyl alcohol with the reduction of methyl benzoate derivative, reacts with cyanide reag...

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): C07D317/64
Inventor 葛敏付明伟
Owner 南京正济医药销售有限公司
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