Beta-amino phosphonic acid derivative and preparation method therefor

Patent metadata

Field	Value
Publication number	US-11401288-B2
Application number	US-202117146729-A
Country	US
Kind code	B2
Filing date	Jan 12, 2021
Priority date	Jul 12, 2018
Publication date	Aug 2, 2022
Grant date	Aug 2, 2022

Abstract

A method for preparing a β-amino phosphonic acid derivative includes: dissolving N-(arylvinyl)benzamide, dialkyl phosphite, manganese acetate, and potassium carbonate in a solvent and reacting at room temperature to obtain (2-benzamido-1-arylvinyl)dialkyl-phosphonate derivative; and hydrolyzing (2-benzamido-1-arylethyl)dialkylphosphonate derivative to obtain β-amino phosphonic acid derivative. The N-(arylvinyl)benzamide derivative is used as starting material. The raw materials are easy to obtain and are of many different types. A method of preparing β-aminophosphonic acid derivative includes: dissolving N-(arylvinyl)benzamide, dialkyl phosphite, manganese acetate and potassium carbonate in a solvent, reacting at room temperature to obtain (2-benzamide-1-arylvinyl) dialkyl phosphonate derivative, and then reducing and hydrolyzing the compound to obtain β-aminophosphonic acid derivative. The method of the invention has the advantages of short synthesis route, mild reaction conditions, simple reaction operation and post-treatment process, good yield, and is suitable for large-scale production.

First claim

The invention claimed is:

1. A method for preparing a β-amino phosphonic acid derivative, which comprises the following steps:
dissolving an N-(arylvinyl)benzamide derivative, a dialkyl phosphite, manganese acetate, and potassium carbonate in a solvent and reacting at room temperature to obtain a (2-benzamido-1-arylvinyl)dialkylphosphonate derivative;
reducing the (2-benzamido-1-arylvinyl)dialkylphosphonate derivative to obtain a (2-benzamido-1-arylethyl)dialkylphosphonate derivative;
hydrolyzing the (2-benzamido-1-arylethyl)dialkylphosphonate derivative to obtain the (3-amino phosphonic acid derivative,
wherein the N-(arylvinyl) benzamide derivative has the following structure:

R is hydrogen, methyl, methoxy, fluorine, chlorine, or bromine;
the dialkyl phosphite has the following structure:

R 1 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl.

2. A method for preparing a (2-benzamido-1-arylethyl)dialkylphosphonate derivative, which comprises the following steps:
dissolving an N-(arylvinyl)benzamide derivative, a dialkyl phosphite, manganese acetate, and potassium carbonate in a solvent and reacting at room temperature to obtain a (2-benzamido-1-arylvinyl)dialkylphosphonate derivative;
reducing the (2-benzamido-1-arylvinyl)dialkylphosphonate derivative to obtain the (2-benzamido-1-arylethyl)dialkylphosphonate derivative;
wherein the N-(arylvinyl)benzamide derivative has the following structure:

R is hydrogen, methyl, methoxy, fluorine, chlorine, or bromine;
the dialkyl phosphite has the following structure:

R 1 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl.

3. The method according to claim 1 , wherein the dialkyl phosphite is selected from the group consisting of dimethyl phosphite, diethyl phosphite, and diisopropyl phosphate; the solvent is selected from the group consisting of methanol, ethanol, acetone, and acetonitrile; the N-(arylvinyl)benzamide derivative is selected from the group consisting of N-(styryl)benzamide, 2 methyl-N-(styryl)benzamide, 2-methoxy-N-(styryl)-benzamide, 2-chloro-N-(styryl)benzamide, 2-fluoro-N-(styryl)benzamide, 2-bromo-N-(styryl)benzamide, 3-methyl-N-(styryl)benzamide, 3-methoxy-N-(styryl)benzamide, 3-chloro-N-(styryl)benzamide, 3-fluoro-N-(styryl)benzamide, 3 bromo-N-(styryl)benzamide, 4-methyl-N-(styryl)benzamide, 4-methoxy-N-(styryl)benzamide, 4-chloro-N-(styryl)benzamide, 4-fluoro-N-(styryl)benzamide, and 4-bromo-N-(styryl)benzamide.

4. The method according to claim 1 , wherein the reaction is tracked to completion by a thin layer chromatography and the reaction is performed at room temperature.

5. The method according to claim 1 , wherein a molar ratio of the N-(arylvinyl)benzamide derivative:the dialkyl phosphite:manganese acetate:potassium carbonate is 1:2:2.5:2.

6. The method according to claim 1 , wherein the (2-benzamido-1-arylvinyl)-dialkylphosphonate derivative is reduced with Raney-Ni/H 2 .

7. The method according to claim 1 , wherein the (2-benzamido-1-arylethyl)dialkyl-phosphonate derivative is hydrolyzed with hydrochloric acid.

8. The method according to claim 2 , wherein the dialkyl phosphite is selected from the group consisting of dimethyl phosphite, diethyl phosphite, and diisopropyl phosphate; the solvent is selected from the group consisting of methanol, ethanol, acetone, and acetonitrile; the N-(arylvinyl)benzamide derivative is selected from the group consisting of N-(styryl)benzamide, 2 methyl-N-(styryl)benzamide, 2-methoxy-N-(styryl)-benzamide, 2-chloro-N-(styryl)benzamide, 2-fluoro-N-(styryl)benzamide, 2-bromo-N-(styryl)benzamide, 3-methyl-N-(styryl)benzamide, 3-methoxy-N-(styryl)benzamide, 3-chloro-N-(styryl)benzamide, 3-fluoro-N-(styryl)benzamide, 3 bromo-N-(styryl)benzamide, 4-methyl-N-(styryl)benzamide, 4-methoxy-N-(styryl)benzamide, 4-chloro-N-(styryl)benzamide, 4-fluoro-N-(styryl)benzamide, and 4-bromo-N-(styryl)benzamide.

9. The method according to claim 2 , wherein the reaction is tracked to completion by a thin layer chromatography and the reaction is performed at room temperature.

10. The method according to claim 2 , wherein a molar ratio of the N-(arylvinyl)benzamide derivative:the dialkyl phosphite:manganese acetate:potassium carbonate is 1:2:2.5:2.

11. The method according to claim 2 , wherein the (2-benzamido-1-arylvinyl)-dialkylphosphonate derivative is reduced with Raney-Ni/H 2 .

Assignees

• Univ Soochow

Inventors

• Zou Jianping
• Zhang Dongliang
• Li Chengkun
• Zhang Guoyu
• Tao Zekun

Classifications

• C07F9/3826

  Acyclic unsaturated acids · CPC title

• C07F9/3882 Primary

  Arylalkanephosphonic acids (C07F9/3839 takes precedence) · CPC title

• B01J25/02

  Raney nickel · CPC title

• C07F9/38 Primary

  Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids {; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]} · CPC title