CN113582842A

CN113582842A - Preparation process of methyl glycolate

Info

Publication number: CN113582842A
Application number: CN202110842111.7A
Authority: CN
Inventors: 汤健志; 刘相国; 蔡蓉蓉
Original assignee: Suzhou Qiusuo Biotechnology Co ltd
Current assignee: Suzhou Qiusuo Biotechnology Co ltd
Priority date: 2021-07-26
Filing date: 2021-07-26
Publication date: 2021-11-02

Abstract

The invention relates to a preparation process of benzyl glycolate, which comprises the following steps: respectively adding an organic solvent and glycolic acid into a three-neck flask, uniformly stirring at a low temperature, adding benzyl bromide while stirring, controlling the reaction temperature to be low, then dropwise adding an organic solution containing organic alkali, controlling the reaction temperature to be low, then heating the solution to room temperature, stirring for reaction for a certain time, then concentrating the solution under reduced pressure to a certain concentration, and finally extracting, drying and desolventizing to obtain colorless liquid benzyl glycolate; the method has mild reaction conditions, the used raw materials are common compounds with low price, and the solvent is evaporated to dryness to obtain a high-purity product, so that the product can be directly put into use without further post-treatment, and the method is very suitable for mass production.

Description

Preparation process of methyl glycolate

Technical Field

The invention relates to the technical field of drug synthesis, in particular to a preparation process of benzyl glycolate.

Background

The glycolic acid benzyl ester is an important intermediate of raw material medicines and is frequently appeared in the synthesis of various new medicines; in the existing synthesis technology, the glycolic acid benzyl ester is mainly obtained by the reaction of raw materials of glycolic acid, benzyl bromide and cesium carbonate, and the synthesis route is as follows:

in the method, the dosage of cesium carbonate is large, the price is high, the cost control is not facilitated, and a large amount of purification work is needed subsequently to obtain a product with high purity, so that the method has certain limitation.

Disclosure of Invention

The invention aims to provide a preparation process of benzyl glycolate by overcoming the defects of the prior art.

In order to achieve the purpose, the invention adopts the technical scheme that: a preparation process of benzyl glycolate comprises the following steps:

s1: respectively adding an organic solvent and glycolic acid into a three-necked flask, uniformly stirring, and controlling the reaction temperature to be low;

s2: adding benzyl bromide into the solution obtained in the step S1 while stirring, and controlling the reaction temperature to be low;

s3: dropping an organic solution containing an organic base into the solution obtained in step S2, and controlling the reaction temperature to be low;

s4: heating the solution obtained in the step S3 to room temperature, and stirring for reaction;

s5: concentrating the solution obtained in step S4 under reduced pressure;

s6: the reaction solution obtained in step S5 was extracted with ethyl acetate, the extracts were combined, and then the extracts were dried with a saturated sodium bicarbonate solution and anhydrous magnesium sulfate in this order, and finally the solvent was evaporated to dryness to obtain colorless liquid benzyl glycolate.

Preferably, in step S1, the organic solvent is one or more of ethanol, acetone, acetonitrile and ethyl acetate.

Preferably, in step S1, the concentration of glycolic acid in the organic solvent is 0.1-1 g/ml.

Preferably, in step S2, the concentration of benzyl bromide is 0.5-5 g/ml.

Preferably, in step S3, the organic base is one or more of sodium hydroxide, triethylamine, potassium hydroxide, and DBU.

Preferably, in step S3, the organic solvent is one or more of ethanol, acetone, acetonitrile and ethyl acetate.

Preferably, in the step S1-S3, the low temperature is-20 to 20 ℃.

Preferably, in the step S4, the stirring reaction time is 8 to 20 hours.

Preferably, in step S5, the volume of the solution after concentration under reduced pressure is 1/2 to 1/5 of the volume of the original reaction solution.

Preferably, in step S6, the extract is dried by saturated sodium bicarbonate solution for several times, and then dried by anhydrous magnesium sulfate.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

the method has mild reaction conditions, the used raw materials are common compounds with low price, and the solvent is evaporated to dryness to obtain a high-purity product, so that the product can be directly put into use without further post-treatment, and the method is very suitable for mass production.

Drawings

The technical scheme of the invention is further explained by combining the accompanying drawings as follows:

FIG. 1 is a liquid phase diagram of benzyl glycolate as described in example 1 of the invention;

FIG. 2 is a liquid phase diagram of benzyl glycolate as described in example 2 of the invention;

FIG. 3 is a liquid phase diagram of benzyl glycolate as described in example 3 of the invention.

Detailed Description

The invention is described in further detail below with reference to the figures and the embodiments.

The first embodiment is as follows:

glycolic acid (10g,0.13mol) and 50ml of absolute ethanol were added in this order to a three-necked flask and stirred until completely clear.

Benzyl bromide (22.23g,0.13mol) was added slowly and the reaction was controlled to 20 ℃ and stirred until completely clear.

A solution of sodium hydroxide (5.20g,0.13mol) in absolute ethanol (10ml) was added dropwise, maintaining the temperature of the system at 20 ℃ until the addition was complete.

The reaction was stirred at room temperature for 10 h.

Distilling under reduced pressure until the volume of the reaction liquid is reduced by half.

The reaction mixture was extracted by adding ethyl acetate (50 ml. times.3), the organic phases were combined, the extract was dried successively with a saturated sodium bicarbonate solution (300 ml. times.4) and anhydrous magnesium sulfate, and the solvent was evaporated to dryness to give 17.69g of colorless liquid benzyl glycolate.

The product obtained in this example has a purity of 93% and a yield of 82%, and the liquid phase diagram is shown in FIG. 1.

Example two:

glycolic acid (10g,0.13mol) and 10ml acetone were added sequentially to a three-necked flask and stirred until completely clear.

Benzyl bromide (22.23g,0.13mol) was added slowly and the reaction was controlled to-10 ℃ and stirred until completely clear.

A solution of triethylamine (13.20g,0.13mol) in acetone (10ml) was added dropwise, maintaining the system temperature at-10 ℃ until the addition was complete.

The reaction was stirred at room temperature for 15 h.

And (4) distilling under reduced pressure until the volume of the reaction liquid is reduced to one third.

The reaction mixture was extracted by adding ethyl acetate (50 ml. times.3), the organic phases were combined, the extract was dried successively with a saturated sodium bicarbonate solution (300 ml. times.4) and anhydrous magnesium sulfate, and the solvent was evaporated to dryness to give 15.11g of benzyl glycolate as a dark yellow liquid.

The product obtained in this example is dark in color, 85% in purity and 70% in yield, and the liquid phase diagram is shown in FIG. 2.

Example three:

glycolic acid (10g,0.13mol) and 70ml acetonitrile were added sequentially to a three-necked flask and stirred until completely clear.

Benzyl bromide (21.58g,0.13mol) was added slowly and the reaction was controlled to 0 ℃ and stirred until completely clear.

A solution of DBU (13.20g,0.13mol) in acetonitrile (10ml) was added dropwise, maintaining the system temperature at 0 ℃ until the addition was complete.

The reaction was stirred at room temperature for 18 h.

And (4) distilling under reduced pressure until the volume of the reaction liquid is reduced to one fifth.

The reaction mixture was extracted by adding ethyl acetate (50 ml. times.3), the organic phases were combined, the extract was dried successively with a saturated sodium bicarbonate solution (300 ml. times.4) and anhydrous magnesium sulfate, and the solvent was evaporated to dryness to give colorless liquid benzyl glycolate 19.85 g.

The purity of the product obtained in this example was 97%, the yield was 92%, and the liquid phase diagram is shown in FIG. 3.

The method has mild reaction conditions, the used raw materials are common compounds with low price, and the solvent is evaporated to dryness to obtain a high-purity product, the high-purity product can be directly put into use without further post-treatment, and the method is very suitable for mass production

The above is only a specific application example of the present invention, and the protection scope of the present invention is not limited in any way. All the technical solutions formed by equivalent transformation or equivalent replacement fall within the protection scope of the present invention.

Claims

1. A preparation process of methyl glycolate, which is characterized by comprising the following steps: comprises the following steps:

s5: concentrating the solution obtained in step S4 under reduced pressure;

2. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S1, the organic solvent is one or more of ethanol, acetone, acetonitrile, and ethyl acetate.

3. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S1, the concentration of the glycolic acid in the organic solvent is 0.1-1 g/ml.

4. The process for producing benzyl glycolate as claimed in claim 1, wherein: in the step S2, the concentration of the benzyl bromide is 0.5-5 g/ml.

5. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S3, the organic base is one or more of sodium hydroxide, triethylamine, potassium hydroxide, and DBU.

6. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S3, the organic solvent is one or more of ethanol, acetone, acetonitrile, and ethyl acetate.

7. The process for the preparation of benzyl glycolate as claimed in any one of claims 1 to 6, characterized in that: in the steps S1-S3, the low temperature is-20 to 20 ℃.

8. The process for producing benzyl glycolate as claimed in claim 1, wherein: in the step S4, the stirring reaction time is 8-20 h.

9. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S5, the volume of the solution after the reduced pressure concentration is 1/2-1/5 of the volume of the original reaction solution.

10. The process for producing benzyl glycolate as claimed in claim 1, wherein: in step S6, the extract needs to be dried by saturated sodium bicarbonate solution several times, and then dried by anhydrous magnesium sulfate.