N-methyldihexanolamine and its preparation method and application

Abstract

The present invention relates to N-methyldihexanolamine and its preparation method and application, belonging to the technical field of preparation of N-methyldihexanolamine. The present invention mainly uses ε-caprolactone and 6-amino-1-hexanol as raw materials, adds lithium aluminum tetrahydride after reaction to generate dihexanolamine, and then reacts with formic acid and formaldehyde and neutralizes with NaOH to obtain. The preparation method of the present invention is simple and easy, the raw materials are easy to obtain, the amount of wastewater generated during the synthesis process of N-methyldihexanolamine can be greatly reduced, and the yield of N-methyldihexanolamine can be greatly improved.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of N-methyldihexanolamine and relates to N-methyldihexanolamine and a preparation method and application thereof. Background Art

[0002] With the improvement of people's living standards, people's requirements for the function and quality of clothing are constantly increasing. Clothing fabrics with bright colors, washability, wrinkle resistance, and skin-friendly comfort are favored by modern young people. However, some pure cotton knitted fabrics, denim and silk fabrics have poor friction fastness and are very easy to fade after washing, which reduces the quality and aesthetic feeling of clothing, giving people the sensory experience of "not resistant to washing and not wanting to wear it after a few times". Related literature reports that modified waterborne polyurethane has an enhanced effect on the fixation of reactive dyes, greatly improving the friction fastness and fading degree of fabrics (Yuhang Wang, He Huan. A Study on the Dye Fixation Mechanism of Waterborne Polyurethane. 2023, 8 (12): e202204620. DOI: 10.1002 / slct.202204620). At present, the market mostly uses small molecular diamines (such as ethylenediamine, etc.) and diols (such as propylene glycol, etc.) as the chain extension system of waterborne polyurethane, which requires more reactants and produces many complex by-products. Therefore, it is necessary to adopt relevant preparation methods to directly obtain compounds with both amino groups and two alcoholic hydroxyl groups as chain extenders or modifiers for the synthesis and modification of waterborne polyurethanes, reduce by-products and purification processes, indirectly improve product purity and reduce reaction energy consumption, such as N-methyldihexanolamine.

[0003] Nitrogen mustards are among the earliest anti-tumor drugs used clinically and have demonstrated remarkable efficacy. For example, nitrogen mustard hydrochloride is primarily used to prevent and treat malignancies such as lung cancer, malignant lymphoma, head and neck cancer, chronic leukemia, and breast cancer. However, due to the high reactivity of nitrogen mustards, most react with proteins and phospholipids within cell membranes. Consequently, only a very small fraction of nitrogen mustards reaches the cell nucleus, alkylating and cross-linking DNA, and achieving a therapeutic effect. Therefore, researchers have attempted to replace the methyl groups on nitrogen mustards with various groups to create more effective anti-tumor drugs.

[0004] N-methyldiethanolamine has been widely used as a synthetic intermediate for anti-tumor drugs (nitrogen mustard hydrochloride). N-methyldihexanolamine adds an active site of 8 carbon atoms to the carbon chain of N-methyldiethanolamine in order to more effectively introduce anti-cancer functional groups and synthesize nitrogen mustard drugs with better efficacy, providing an effective strategy for the treatment of various cancers. Summary of the Invention

[0005] In view of this, an object of the present invention is to provide N-methyldihexanolamine; a second object of the present invention is to provide a method for preparing N-methyldihexanolamine; and a third object of the present invention is to provide the use of N-methyldihexanolamine in the preparation of anti-tumor nitrogen mustard drugs.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] 1. N-methyldiethanolamine, the structural formula of the N-methyldiethanolamine is

[0008]

[0009] 2. The preparation method of the above-mentioned N-methyldihexanolamine comprises the following steps:

[0010] (1) adding ε-caprolactone and 6-amino-1-hexanol to a solvent to dissolve and form a first premix, heating the first premix to 100-150° C. and reacting for 12-36 hours to obtain a first reaction product;

[0011] (2) Purifying the first reactant prepared in step (1) by column chromatography to obtain a second reactant, adding the second reactant and lithium aluminum tetrahydride into a solvent to dissolve to form a second premix, heating the second premix to 80-120° C. and reacting for 18-36 hours to obtain a second reaction product;

[0012] (3) centrifuging the second reaction product prepared in step (2) and subjecting it to column chromatography to obtain dihexanolamine, adding dihexanolamine, formic acid, and formaldehyde to a solvent to dissolve them to form a third premix, heating the third premix to 80-100° C. and reacting for 18-36 hours to obtain a third reaction product;

[0013] (4) The third reaction product prepared in step (3) is subjected to a neutralization reaction and then subjected to column chromatography to obtain N-methyldihexanolamine.

[0014] Preferably, in step (1), the solvent is toluene.

[0015] Preferably, in step (1), the molar ratio of ε-caprolactone to 6-amino-1-hexanol is 1:1 to 1:1.5;

[0016] The volume ratio of the ε-caprolactone to the solvent is 1:10-12.

[0017] Preferably, in step (2), the molar ratio of lithium aluminum tetrahydride to the second reactant is 1:4 to 1:6;

[0018] In step (2), the solvent is dry tetrahydrofuran, wherein the volume of the solvent is more than 10 times the total volume of the second reactant and lithium aluminum tetrahydride.

[0019] Preferably, in step (2) and step (3), the mobile phase used in the column chromatography purification is a mixed solution of methanol and ethyl acetate in a volume ratio of 1:1 to 1:2.

[0020] Preferably, in step (3), the molar ratio of formaldehyde, formic acid and dihexanolamine is 8:9:1 to 10:15:1;

[0021] In step (3), the solvent is ethanol, wherein the volume of the solvent is 10 to 15 times the total volume of dihexanolamine, formic acid and formaldehyde.

[0022] Preferably, in step (4), the neutralization reaction is performed by adding a NaOH solution with a mass fraction of 5% to 10% to the third reaction product, wherein the mass ratio of the third reaction product to NaOH in the NaOH solution is 1:3 to 1:8.

[0023] Preferably, in step (4), the mobile phase used in the column layer treatment is a mixed solution of methanol and ethyl acetate in a volume ratio of 1:2 to 1:5.

[0024] 3. Use of the above-mentioned N-methyldihexanolamine in the preparation of anti-tumor nitrogen mustard drugs.

[0025] The present invention provides N-methyldihexanolamine, its preparation method, and application. The invention primarily utilizes ε-caprolactone and 6-amino-1-hexanol as raw materials. After the reaction, lithium aluminum tetrahydride is added to generate dihexanolamine, which is then reacted with formic acid and formaldehyde and neutralized with sodium hydroxide. The preparation method is simple and easy to implement, utilizes readily available raw materials, significantly reduces wastewater generation during the synthesis of N-methyldihexanolamine, and significantly improves the yield of N-methyldihexanolamine. The N-methyldihexanolamine prepared by the present invention has promising application prospects in the preparation of anti-tumor nitrogen mustard drugs.

[0026] Other advantages, objects, and features of the present invention will be described in part in the following description and, in part, will be apparent to those skilled in the art upon examination of the following description or may be learned from practice of the present invention. The objects and other advantages of the present invention may be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be described in detail below with reference to the accompanying drawings, in which:

[0028] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the intermediate dihexanolamine prepared in Example 1 of the present invention;

[0029] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the product N-methyldihexanolamine prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The following describes the embodiments of the present invention by means of specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the illustrations provided in the following embodiments are only schematic illustrations of the basic concept of the present invention, and the following embodiments and features in the embodiments can be combined with each other without conflict.

[0031] The synthetic route of N-methyldiethanolamine preparation method of the present invention is expressed as follows:

[0032]

[0033] Example 1

[0034] The preparation method of N-methyldihexanolamine specifically comprises the following steps:

[0035] (1) 12 g of ε-caprolactone (0.105 mol) and 12.5 g of 6-amino-1-hexanol (0.106 mol) were added to a 500 ml round-bottom flask, and toluene (wherein the volume ratio of ε-caprolactone to toluene was 1:11) was added under stirring to dissolve the mixture to form a first premix. The mixture was heated to 120° C. at a speed of 300 r / min and refluxed for 24 h. After the reaction was completed, the mixture was dried by rotary evaporation to obtain a first reaction product.

[0036] (2) The first reactant prepared in step (1) was purified by column chromatography to obtain 15 g of the second reactant (35 g of silica gel was added to the first reactant prepared in step (1) at a mass of 1.5 times, and methanol was added to dissolve the resulting paste, which was then placed on a rotary evaporator to be fully mixed; about 2 / 5 of silica gel was added to the chromatography column, and then the silica gel product mixture obtained by rotary evaporation was added, and about 1 cm thick quartz sand was spread on the upper layer (the volume ratio of the mobile phase: methanol and ethyl acetate was 1:1, and the mixture was slowly added to the chromatography column, and an air pump was connected to the top of the chromatography column to allow the mobile phase to gradually pass through the stationary phase). The effluent was collected, the first 15 ml was discarded, and then about 15 ml of the effluent was collected in the order of outflow. The plate was found to be all products, and the color on the silica gel plate was very light until the sixteenth tube, indicating that there was very little product at this time. The collection was continued until No product spot can be seen after the dot plate; the collected pure product is repeatedly and a small amount is spin-dried on a rotary evaporator, and after all the rotary evaporations are completed, it is placed in a vacuum drying oven for drying); the light yellow liquid obtained after the above purification is added to a 500ml three-necked flask (the second reaction product), lithium aluminum hydride is added at a mass ratio of 1:5 (lithium aluminum hydride is added in small amounts and multiple times in an ice-water bath), and then dry tetrahydrofuran is added (wherein the volume of dry tetrahydrofuran is more than 10 times the total volume of the second reactant and lithium aluminum hydride) to make them miscible, and after heating to 80°C at a speed of 250r / min, the reaction is refluxed for 20h, and deionized water is added dropwise to the flask after the above reaction in an ice-water bath in small amounts and multiple times to dissolve the product until it is completely dissolved and the solution is milky white. The supernatant is collected and the precipitate is recovered to a waste liquid bucket; the supernatant is collected and rotary evaporated and dried to obtain the second reaction product;

[0037] (3) The second reaction product prepared in step (2) was subjected to column chromatography after centrifugation (silica gel was added to the second reaction product at a mass ratio of 1.5 times, and then 90g of methanol was added and the mixture was rotary evaporated; about 2 / 5 silica gel was added to the chromatography column, and then the silica gel product mixture that had been rotary evaporated was added, and quartz sand of about 1cm thick was spread on the upper layer, and a mobile phase with a volume ratio of methanol and ethyl acetate of 1:1 was prepared and slowly added to the chromatography column, and an air pump was connected above the chromatography column to allow the mobile phase to gradually pass through the stationary phase; the effluent was collected, and then about 15ml of the liquid was successively added to the test tube, and the plate was plated until the effluent was a pure substance, and the collected liquid was rotary evaporated and dried) to obtain dihexanolamine (the results of the nuclear magnetic resonance hydrogen spectrum analysis were as follows: Figure 1 ), 3.5 g of dihexanolamine (0.0333 mol) prepared above was added to a 500 ml round-bottom flask, and 15.31 g of formic acid (0.333 mol), 9.99 g of formaldehyde (0.333 mol) and ethanol (wherein the volume of ethanol is 12 times the total volume of dihexanolamine, formic acid and formaldehyde) were added under stirring, and the mixture was heated to 80° C. at a speed of 200 r / min, and refluxed in an oil bath for 24 h to obtain a third reaction product;

[0038] (4) A 5% mass fraction of NaOH solution was added to the three-reaction product prepared in step (3) until the pH value of the solution was 7 for neutralization. The neutralized solution was extracted with dichloromethane in small amounts and multiple times for 3-5 times, with the organic phase in the lower layer and the aqueous phase in the upper layer. The extracted organic phase and the aqueous phase were separated and stored, and then the organic phase was rotary evaporated to obtain 3.5 g of the product, which was purified by column chromatography (silica gel and 30 ml of methanol were added according to 2 times the mass for rotary evaporation, an appropriate amount of silica gel was added to the chromatography column, and then the rotary evaporated product was added, and quartz sand of about 1 cm thick was spread on the upper layer; a mobile phase with a volume ratio of methanol and ethyl acetate of 1:3 was prepared and slowly added to the chromatography column. An air pump was connected above the chromatography column to allow the mobile phase to gradually pass through the stationary phase. The plate was used to distinguish the pure substances before and after the reaction, and the effluent was collected) to obtain N-methyldihexanolamine (NMR hydrogen spectrum detection was as follows) Figure 2 The yield was 85%.

[0039] Example 2

[0040] The preparation method of N-methyldihexanolamine specifically comprises the following steps:

[0041] (1) 12 g of ε-caprolactone (0.105 mol) and 18.46 g of 6-amino-1-hexanol (0.1575 mol) were added to a 500 ml round-bottom flask, and toluene (wherein the volume ratio of ε-caprolactone to toluene was 1:10) was added under stirring to dissolve to form a first premix. The mixture was heated to 100° C. at a speed of 300 r / min and refluxed for 36 h. After the reaction was completed, the mixture was dried by rotary evaporation to obtain a first reaction product.

[0042] (2) The first reactant prepared in step (1) is purified by column chromatography to obtain a second reactant (35 g of silica gel is added to the first reactant prepared in step (1) at a mass of 1.5 times, methanol is added to dissolve to obtain a paste-like substance, and the paste is placed on a rotary evaporator to be fully mixed; about 2 / 5 silica gel is added to the chromatography column, and then the silica gel product mixture evaporated from the rotary evaporator is added, and quartz sand about 1 cm thick is spread on the upper layer (the volume ratio of mobile phase: methanol and ethyl acetate is 1:2, and it is slowly added to the chromatography column, and an air pump is connected to the top of the chromatography column to allow the mobile phase to gradually pass through the stationary phase) The effluent is collected, the first 15 ml is discarded, and then about 15 ml of the effluent is collected in the order of outflow. The plate is found to be all products. Until the sixteenth tube, the color on the silica gel plate is very light, indicating that there is very little product at this time. Continue to collect until the plate is pointed. After that, no product point can be seen; the collected pure product is repeatedly dried in a small amount on a rotary evaporator, and after all the rotary evaporations are completed, it is placed in a vacuum drying oven for drying), the light yellow liquid obtained after the above purification is added to a 500ml three-necked flask (the second reaction product), lithium aluminum hydride is added at a mass ratio of 1:4 (lithium aluminum hydride is added in small amounts and multiple times in an ice-water bath), and then dry tetrahydrofuran is added (wherein the volume of dry tetrahydrofuran is more than 10 times the total volume of the second reactant and lithium aluminum hydride) to make them miscible, and after heating to 80°C at a speed of 250r / min, the reaction is refluxed for 36h, and deionized water is added dropwise to the flask after the above reaction in a small amount and multiple times in an ice-water bath to dissolve the product until it is completely dissolved and the solution is milky white. The supernatant is collected and the precipitate is recovered to a waste liquid bucket; the supernatant is collected and rotary evaporated and dried to obtain the second reaction product;

[0043] (3) The second reaction product prepared in step (2) was subjected to column chromatography after centrifugation (silica gel was added to the second reaction product at a mass ratio of 1.5 times, and 90g of methanol was added and then rotary evaporated to mix; about 2 / 5 silica gel was added to the chromatography column, and then the silica gel product mixture that had been rotary evaporated was added, and quartz sand of about 1cm thick was spread on the upper layer, and a mobile phase with a volume ratio of methanol and ethyl acetate of 1:2 was prepared and slowly added to the chromatography column, and an air pump was connected above the chromatography column to allow the mobile phase to gradually pass through the stationary phase; the effluent was collected, and then about 15ml of the effluent was successively added to the test tube. liquid, and the plate was placed until the outflowing liquid was a pure substance, the collected liquid was rotary evaporated and dried) to obtain dihexanolamine, and 3.5 g of dihexanolamine (0.0333 mol) prepared above was added to a 500 ml round-bottom flask, and 13.78 g of formic acid (0.2996 mol), 7.99 g of formaldehyde (0.266 mol) and ethanol (wherein the volume of ethanol is 10 times the total volume of dihexanolamine, formic acid and formaldehyde) were added under stirring, and heated to 80 ° C at a speed of 200 r / min, and refluxed in an oil bath for 36 h to obtain a third reaction product;

[0044] (4) A 5% by mass NaOH solution was added to the three-reaction product prepared in step (3) until the pH value of the solution was 7 for neutralization. The neutralized solution was extracted with dichloromethane in small amounts for 3-5 times, with the organic phase in the lower layer and the aqueous phase in the upper layer. The extracted organic phase and the aqueous phase were separated and stored. The organic phase was then rotary evaporated to obtain 3.5 g of the product, which was purified by column chromatography (silica gel and 30 ml of methanol were added according to 2 times the mass for rotary evaporation. An appropriate amount of silica gel was added to the chromatography column, and the rotary evaporated product was added. Quartz sand of about 1 cm thick was spread on the upper layer; a mobile phase of methanol and ethyl acetate in a volume ratio of 1:2 was prepared and slowly added to the chromatography column. An air pump was connected to the top of the chromatography column to allow the mobile phase to gradually pass through the stationary phase. A plate was placed to distinguish the pure substances before and after the reaction, and the effluent was collected). N-methyldihexanolamine was obtained with a yield of 70%.

[0045] Example 3

[0046] A method for preparing N-methyldihexanolamine specifically comprises the following steps:

[0047] (1) 12 g of ε-caprolactone (0.105 mol) and 14.77 g of 6-amino-1-hexanol (0.126 mol) were added to a 500 ml round-bottom flask, and toluene (wherein the volume ratio of ε-caprolactone to toluene was 1:12) was added under stirring to dissolve the mixture to form a first premix. The mixture was heated to 150° C. at a speed of 300 r / min and refluxed for 12 h. After the reaction was completed, the mixture was dried by rotary evaporation to obtain a first reaction product.

[0048] (2) The first reactant prepared in step (1) was purified by column chromatography to obtain a second reactant (35 g of silica gel was added to the first reactant prepared in step (1) at a mass of 1.5 times, and 50 g of methanol was added to dissolve the obtained paste, which was then placed on a rotary evaporator to be fully mixed; about 2 / 5 of silica gel was added to the chromatography column, and then the silica gel product mixture obtained by rotary evaporation was added, and about 1 cm thick quartz sand was spread on the upper layer (the volume ratio of mobile phase: methanol and ethyl acetate was 1:1, and the mixture was slowly added to the chromatography column, and an air pump was connected to the top of the chromatography column to allow the mobile phase to gradually pass through the stationary phase) and the effluent was collected, the first 15 ml was discarded, and then about 15 ml of the effluent was collected in the order of outflow. The plate was found to be all products, and the color on the silica gel plate was very light until the sixteenth tube, indicating that there was very little product at this time. The effluent was collected until the plate was found to be all products. No product point can be seen after the plate; the collected pure product is repeatedly dried in a small amount on a rotary evaporator, and after all the rotary evaporation is good, it is placed in a vacuum drying oven for drying), the light yellow liquid obtained after the above purification is added to a 500ml three-necked flask (the second reaction product), lithium aluminum hydride is added at a mass ratio of 1:6 (lithium aluminum hydride is added in small amounts and multiple times in an ice-water bath), and then dry tetrahydrofuran is added (wherein the volume of dry tetrahydrofuran is more than 10 times the total volume of the second reactant and lithium aluminum hydride) to make them miscible, and after heating to 120°C at a speed of 250r / min, reflux for 18h, deionized water is added dropwise to the flask after the above reaction in an ice-water bath in small amounts and multiple times to dissolve the product until it is completely dissolved and the solution is milky white, the supernatant is collected, and the precipitate is recovered to a waste liquid bucket; the supernatant is collected and rotary evaporated and dried to obtain the second reaction product;

[0049] (3) The second reaction product prepared in step (2) was subjected to column chromatography after centrifugation (silica gel was added to the second reaction product at a mass ratio of 1.5 times, and 90 g of methanol was added and then rotary evaporated to mix; about 2 / 5 silica gel was added to the chromatography column, and then the silica gel product mixture that had been rotary evaporated was added, and quartz sand of about 1 cm thick was spread on the upper layer, and a mobile phase with a volume ratio of methanol and ethyl acetate of 1:1 was prepared and slowly added to the chromatography column, and an air pump was connected above the chromatography column to allow the mobile phase to gradually pass through the stationary phase; the effluent was collected, and then about 15 ml of the effluent was successively added to the test tube. liquid, and the plate was tapped until the outflowing liquid was a pure substance, the collected liquid was rotary evaporated and dried) to obtain dihexanolamine, and 3.5 g of dihexanolamine (0.0333 mol) prepared above was added to a 500 ml round-bottom flask, and 22.97 g of formic acid (0.499 mol), 9.99 g of formaldehyde (0.333 mol) and ethanol (wherein the volume of ethanol is 15 times the total volume of dihexanolamine, formic acid and formaldehyde) were added under stirring, and heated to 100 ° C at a speed of 200 r / min, and refluxed in an oil bath for 18 h to obtain a third reaction product;

[0050] (4) A 5% by mass NaOH solution was added to the three-reaction product prepared in step (3) until the pH value of the solution was 7 for neutralization. The neutralized solution was extracted with dichloromethane in small amounts for 3-5 times, with the organic phase in the lower layer and the aqueous phase in the upper layer. The extracted organic phase and the aqueous phase were separated and stored. The organic phase was then rotary evaporated to obtain 3.5 g of the product, which was purified by column chromatography (silica gel and 30 ml of methanol were added according to 2 times the mass for rotary evaporation. An appropriate amount of silica gel was added to the chromatography column, and the rotary evaporated product was added. Quartz sand of about 1 cm thick was spread on the upper layer. A mobile phase with a volume ratio of methanol and ethyl acetate of 1:5 was prepared and slowly added to the chromatography column. An air pump was connected to the top of the chromatography column to allow the mobile phase to gradually pass through the stationary phase. A plate was placed to distinguish the pure substances before and after the reaction, and the effluent was collected). N-methyldihexanolamine was obtained with a yield of 80%.

[0051] Similarly, the intermediate product dihexanolamine and the final product N-methyldihexanolamine in the preparation process of Example 2 and Example 3 were subjected to nuclear magnetic hydrogen spectrum analysis, and their structural formula is The result is the same as that of the standard H NMR spectrum, which proves that N-methyldihexanolamine can indeed be prepared by the method of the present invention.

[0052] In summary, the present invention discloses N-methyldihexanolamine, its preparation method, and application. The invention primarily utilizes ε-caprolactone and 6-amino-1-hexanol as raw materials. After the reaction, lithium aluminum tetrahydride is added to generate dihexanolamine, which is then reacted with formic acid and formaldehyde before being neutralized with NaOH. The preparation method of the present invention is simple and easy to implement, utilizes readily available raw materials, significantly reduces wastewater generation during the synthesis of N-methyldihexanolamine, and significantly increases the yield of N-methyldihexanolamine (the yield of N-methyldihexanolamine in the present invention is 70-85%).

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for preparing N-methyldihexanolamine, characterized in that: The preparation method comprises the following steps: (1) adding ε-caprolactone and 6-amino-1-hexanol to a solvent to dissolve and form a first premix, heating the first premix to 100-150° C. and reacting for 12-36 hours to obtain a first reaction product; (2) Purifying the first reactant prepared in step (1) by column chromatography to obtain a second reactant, adding the second reactant and lithium aluminum tetrahydride into a solvent to dissolve to form a second premix, heating the second premix to 80-120° C. and reacting for 18-36 hours to obtain a second reaction product; (3) centrifuging the second reaction product prepared in step (2) and subjecting it to column chromatography to obtain dihexanolamine, adding dihexanolamine, formic acid, and formaldehyde to a solvent to dissolve them to form a third premix, heating the third premix to 80-100° C. and reacting for 18-36 hours to obtain a third reaction product; (4) The third reaction product prepared in step (3) is subjected to a neutralization reaction and then subjected to column chromatography to obtain N-methyldihexanolamine.

2. The preparation method according to claim 1, characterized in that In step (1), the solvent is toluene.

3. The preparation method according to claim 1, characterized in that In step (1), the molar ratio of ε-caprolactone to 6-amino-1-hexanol is 1:1 to 1:1.5; The volume ratio of the ε-caprolactone to the solvent is 1:10-12.

4. The preparation method according to claim 1, characterized in that In step (2), the molar ratio of lithium aluminum tetrahydride to the second reactant is 1:4 to 1:6; In step (2), the solvent is dry tetrahydrofuran, wherein the volume of the solvent is more than 10 times the total volume of the second reactant and lithium aluminum tetrahydride.

5. The preparation method according to claim 1, characterized in that In step (2) and step (3), the mobile phase used in the column chromatography purification is a mixed solution of methanol and ethyl acetate in a volume ratio of 1:1 to 1:

2.

6. The preparation method according to claim 1, characterized in that In step (3), the molar ratio of formaldehyde, formic acid and dihexanolamine is 8:9:1 to 10:15:1; In step (3), the solvent is ethanol, wherein the volume of the solvent is 10 to 15 times the total volume of dihexanolamine, formic acid and formaldehyde.

7. The preparation method according to claim 1, characterized in that In step (4), the neutralization reaction is performed by adding a NaOH solution with a mass fraction of 5% to 10% to the third reaction product for reaction, wherein the mass ratio of the third reaction product to NaOH in the NaOH solution is 1:3 to 1:

8.

8. The preparation method according to claim 1, characterized in that In step (4), the mobile phase used in the column layer treatment is a mixed solution of methanol and ethyl acetate in a volume ratio of 1:2 to 1:5.

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