阅读说明：本技术 一种2-((3,4-双(苄氧基)苄基)氨基)乙醇的合成方法 (Synthetic method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol ) 是由 石博 柴博 柴宁 柴岩 于 2021-11-22 设计创作，主要内容包括：本发明属于化工合成的技术领域,提供了一种2-((3,4-双(苄氧基)苄基)氨基)乙醇的合成方法,增加3,4-二苄氧基苯甲醛上羰基活性,保证乙醇胺上胺基的碱性游离度,从而促进反应,提高收率至60%以上；采用的技术方案为：合成方法包括以下步骤：(1)将原料、催化剂及溶剂加入反应容器中,(2)加料结束后,对反应容器进行加热,(3)停止加热,将反应容器内部降温并进行催化剂过滤,(4)加入硼氢化钠,加完后升温,(5)在反应液中加水,然后减压蒸馏出溶剂,溶剂蒸发完后,再加入乙酸乙酯,萃取,(6)乙酸乙酯相经无水硫酸钠干燥后,过滤,旋蒸,最终获得产品2-((3,4-双(苄氧基)苄基)氨基)乙醇。(The invention belongs to the technical field of chemical synthesis, and provides a synthetic method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol, which increases the carbonyl activity on 3, 4-dibenzyloxy benzaldehyde, and ensures the alkaline freeness of the amino group on ethanolamine, thereby promoting the reaction and improving the yield to more than 60%; the technical scheme is as follows: the synthesis method comprises the following steps: (1) adding raw materials, a catalyst and a solvent into a reaction vessel, (2) heating the reaction vessel after the addition is finished, (3) stopping heating, cooling the interior of the reaction vessel, filtering the catalyst, (4) adding sodium borohydride, heating after the addition is finished, (5) adding water into a reaction solution, then distilling the solvent under reduced pressure, adding ethyl acetate after the solvent is evaporated, extracting, (6) drying an ethyl acetate phase by anhydrous sodium sulfate, filtering, and performing rotary evaporation to finally obtain a product 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol.)

1. A method for synthesizing 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol is characterized by comprising the following steps:

(1) adding a raw material, a catalyst and a solvent into a reaction container, wherein the raw material is 3, 4-dibenzyloxybenzaldehyde and ethanolamine, the catalyst is one of potassium carbonate and sodium carbonate, and the solvent is one of methanol and ethanol;

(2) after the feeding is finished, heating the reaction container, keeping the temperature inside the reaction container at 30-70 ℃, and reacting for 8-24 hours;

(3) stopping heating, reducing the temperature inside the reaction container to-5-10 ℃, and filtering the catalyst of the solution after reaction;

(4) adding sodium borohydride into the filtered reaction solution at the temperature of-5-10 ℃, heating to 20-40 ℃ after the sodium borohydride is added, and keeping the reaction for 6-18 hours at the temperature;

(5) adding water into the reaction solution, then distilling the solvent under reduced pressure, adding ethyl acetate after the solvent is evaporated, and extracting;

(6) and drying the ethyl acetate phase by using anhydrous sodium sulfate, filtering, and performing rotary evaporation to finally obtain the product 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol.

2. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: in the step (1), the weight of the solvent is 1-30 times of that of the 3, 4-dibenzyloxy benzaldehyde.

3. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: the molar ratio of the 3, 4-dibenzyloxybenzaldehyde to the ethanolamine in the step (1) is 1: 1-1: 3.

4. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: the molar ratio of the catalyst to the 3, 4-dibenzyloxybenzaldehyde in the step (1) is 0.1: 1-2: 1.

5. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: the molar ratio of the sodium borohydride to the 3, 4-dibenzyloxybenzaldehyde in the step (4) is 1: 1-8: 1.

6. The method of claim 5, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: and (4) adding sodium borohydride in batches, and controlling the generated foam of the reaction liquid not to overflow the reaction container.

7. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: and (5) adding water in an amount which is 0.5-5 times of the amount of the solvent.

8. The method of claim 1, wherein the synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises: and (5) the using amount of the ethyl acetate is 1-6 times of the water adding amount.

Technical Field

The invention relates to a synthetic method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol, belongs to the technical field of chemical synthesis, and particularly relates to a synthetic method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol.

Background

2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol structural formula:

the molecular formula is as follows: c₂₃H₂₅NO₃

Molecular weight: 363.45

CAS NO.:500899-98-9

The application is as follows: pharmaceutical intermediate

The synthesis of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol involves a relatively small amount of literature and information, and a direct reaction of 3, 4-dibenzyloxybenzaldehyde and ethanolamine was used, but the yield was low, namely 28%.

Disclosure of Invention

The invention overcomes the defects of the prior art, and solves the technical problems that: the synthesis method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol is provided, the carbonyl activity on 3, 4-dibenzyloxybenzaldehyde is increased, and the alkaline freeness of the amino on ethanolamine is ensured, so that the reaction is promoted, and the yield is increased to more than 60%.

In order to solve the technical problems, the invention adopts the technical scheme that: a method for synthesizing 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol comprises the following steps:

(1) adding a raw material, a catalyst and a solvent into a reaction container, wherein the raw material is 3, 4-dibenzyloxybenzaldehyde and ethanolamine, the catalyst is one of potassium carbonate and sodium carbonate, and the solvent is one of methanol and ethanol;

(2) after the feeding is finished, heating the reaction container, keeping the temperature inside the reaction container at 30-70 ℃, and reacting for 8-24 hours;

(3) stopping heating, reducing the temperature inside the reaction container to-5-10 ℃, and filtering the catalyst of the solution after reaction;

(4) adding sodium borohydride into the filtered reaction solution at the temperature of-5-10 ℃, heating to 20-40 ℃ after the sodium borohydride is added, and keeping the reaction for 6-18 hours at the temperature;

(5) adding water into the reaction solution, then distilling the solvent under reduced pressure, adding ethyl acetate after the solvent is evaporated, and extracting;

(6) and drying the ethyl acetate phase by using anhydrous sodium sulfate, filtering, and performing rotary evaporation to finally obtain the product 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol.

In the step (1), the weight of the solvent is 1-30 times of that of the 3, 4-dibenzyloxy benzaldehyde.

The molar ratio of the 3, 4-dibenzyloxybenzaldehyde to the ethanolamine in the step (1) is 1: 1-1: 3.

The molar ratio of the catalyst to the 3, 4-dibenzyloxybenzaldehyde in the step (1) is 0.1: 1-2: 1.

The molar ratio of the sodium borohydride to the 3, 4-dibenzyloxybenzaldehyde in the step (4) is 1: 1-8: 1.

And (4) adding sodium borohydride in batches, and controlling the generated foam of the reaction liquid not to overflow the reaction container.

And (5) adding water in an amount which is 0.5-5 times of the amount of the solvent.

And (5) the using amount of the ethyl acetate is 1-6 times of the water adding amount.

Compared with the prior art, the invention has the beneficial effects that: the method adopts inorganic alkali potassium carbonate or sodium carbonate with proper alkalinity as a catalyst, increases the carbonyl activity on the 3, 4-dibenzyloxy benzaldehyde, and ensures the alkaline freeness of the amine group on the ethanolamine, thereby promoting the reaction and improving the yield to more than 60%; the inorganic base sodium carbonate or potassium carbonate has low solubility in methanol or ethanol, so that the inorganic base sodium carbonate or potassium carbonate can be directly removed by filtration after the catalytic reaction is finished, and the post-treatment trouble of the reduction reaction is reduced.

Detailed Description

The invention relates to a synthetic method of 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol, which comprises the following steps:

(1) adding a raw material, a catalyst and a solvent into a reaction container, wherein the raw material is 3, 4-dibenzyloxybenzaldehyde and ethanolamine, the catalyst is one of potassium carbonate and sodium carbonate, and the solvent is one of methanol and ethanol;

(2) after the feeding is finished, heating the reaction container, keeping the temperature inside the reaction container at 30-70 ℃, and reacting for 8-24 hours;

(3) stopping heating, reducing the temperature inside the reaction container to-5-10 ℃, and filtering the catalyst of the solution after reaction;

(4) adding sodium borohydride into the filtered reaction solution at the temperature of-5-10 ℃, heating to 20-40 ℃ after the sodium borohydride is added, and keeping the reaction for 6-18 hours at the temperature;

(5) adding water into the reaction solution, then distilling the solvent under reduced pressure, adding ethyl acetate after the solvent is evaporated, and extracting;

(6) and drying the ethyl acetate phase by using anhydrous sodium sulfate, filtering, and performing rotary evaporation to finally obtain the product 2- ((3, 4-bis (benzyloxy) benzyl) amino) ethanol.

In the step (1), the weight of the solvent is 1-30 times of that of the 3, 4-dibenzyloxy benzaldehyde.

The molar ratio of the 3, 4-dibenzyloxybenzaldehyde to the ethanolamine in the step (1) is 1: 1-1: 3.

The molar ratio of the catalyst to the 3, 4-dibenzyloxybenzaldehyde in the step (1) is 0.1: 1-2: 1.

The molar ratio of the sodium borohydride to the 3, 4-dibenzyloxybenzaldehyde in the step (4) is 1: 1-8: 1.

And (4) adding sodium borohydride in batches, and controlling the generated foam of the reaction liquid not to overflow the reaction container.

And (5) adding water in an amount which is 0.5-5 times of the amount of the solvent.

And (5) the using amount of the ethyl acetate is 1-6 times of the water adding amount.

The invention adopts inorganic alkali potassium carbonate or sodium carbonate with proper alkalinity as a catalyst, increases the carbonyl activity on the 3, 4-dibenzyloxy benzaldehyde, and ensures the alkaline freeness of the amine group on the ethanolamine, thereby promoting the reaction and improving the yield to more than 60%. The inorganic base sodium carbonate or potassium carbonate has low solubility in methanol or ethanol, so that the inorganic base sodium carbonate or potassium carbonate can be directly removed by filtration after the catalytic reaction is finished, and the post-treatment trouble of the reduction reaction is reduced.

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention; all other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Adding 20g of 3, 4-dibenzyloxybenzaldehyde, 100g of methanol, 5g of ethanolamine and 3.4g of sodium carbonate into a reaction vessel, stirring, heating to 50 ℃ for reaction for 20 hours, cooling to 0 ℃, filtering the sodium carbonate, adding filtrate into a reaction bottle, cooling, adding 4.8g of sodium borohydride in batches at 0-5 ℃, heating to 30 ℃ after the addition, and reacting for 10 hours. Adding 100g of water, decompressing and steaming to remove methanol, extracting with ethyl acetate for three times, 60mL each time, combining ethyl acetate phases, drying with anhydrous sodium sulfate, filtering, decompressing and rotary steaming to dry to obtain 13.8g of a product with the yield of 60.4%.

Example 2

Adding 20g of 3, 4-dibenzyloxybenzaldehyde, 100g of ethanol, 5g of ethanolamine and 4.4g of potassium carbonate into a reaction vessel, stirring, heating to 60 ℃ for reaction for 20 hours, cooling to 0 ℃, filtering the potassium carbonate, adding filtrate into a reaction bottle, cooling, adding 4.8g of sodium borohydride in batches at 0-5 ℃, heating to 35 ℃ after the addition, and reacting for 12 hours. Adding 100g of water, decompressing and steaming to remove ethanol, extracting with ethyl acetate for three times, 60mL each time, combining ethyl acetate phases, drying with anhydrous sodium sulfate, filtering, decompressing and rotary-steaming to dry to obtain 14.2g of a product, wherein the yield is 62.2%.

In the step (4), gas is released when sodium borohydride is added into the reaction liquid, so that the reaction liquid foams, and excessive foam overflows when all sodium borohydride is added at one time, so that the sodium borohydride is added in batches to avoid foam overflow.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.