KR102357197B1 - A preparing method of diethylamino hydroxybenzoyl hexylbenzoate - Google Patents

Abstract

The present invention relates to a method for preparing diethylaminohydroxybenzoylhexylbenzoate, and specifically, to a method for preparing diethylaminohydroxybenzoylhexylbenzoate, which is easy to manufacture and commercially mass-produced, and diethylaminohydroxybenzoylhexylbenzoate prepared by the method Ethylaminohydroxybenzoylhexylbenzoate relates to crystalline particles.
According to the present invention, diethylaminohydroxybenzoylhexylbenzoate crystalline particles having excellent UV blocking effect can be obtained in a stable and high yield.

Description

Method for preparing diethylaminohydroxybenzoylhexylbenzoate {A preparing method of diethylamino hydroxybenzoyl hexylbenzoate}

The present invention relates to a method for producing diethylaminohydroxybenzoylhexylbenzoate, and more particularly, to a method for producing diethylaminohydroxybenzoylhexylbenzoate that is easy to manufacture and can be mass-produced commercially, diethylaminohydroxy It relates to a method for preparing crystalline particles of benzoylhexylbenzoate and to diethylaminohydroxybenzoylhexylbenzoate prepared thereby.

All ultraviolet rays, including those contained in sunlight, are carcinogens. The International Agency for Research on Cancer (IARC) classifies all types of ultraviolet radiation as a group 1 carcinogen, that is, a substance that has been confirmed to cause cancer.

In addition to carcinogenicity, UV rays damage the skin, eyes and immune system, and cause skin aging. Theoretically, it is said that aging is delayed 27 times without UV exposure. In particular, UV-B (320 nm ~ 280 nm), which is abundant in sunlight, causes burns, and UV-C (280 nm ~ 100 nm) used for UV sterilization has high energy, so it is More harmful than UV-B. And UV-A, which was previously known to be harmless, also has high energy, so it was found that DNA damage through free radicals was possible. Burning of the skin when exposed to sunlight is a phenomenon that occurs to protect the skin from harmful substances. In addition to health damage such as skin aging and skin damage, UV rays also cause cosmetic damage such as freckles and spots.

As mentioned above, UV rays are considered the main culprits of various aging and wrinkles, so sunscreens are recommended for all ages. Sunscreens are divided into physical blockers and chemical blockers. Physical blockers mainly use inorganic compounds that reflect UV rays (inorganic blockers), and chemical blockers use a composition that converts UV energy into heat and emits it. (organic blockers).

As inorganic blocking agents, titanium dioxide (titanium dioxide) and zinc oxide are mainly used. Although the blocking effect is excellent, the application is rather stiff, and there is a problem that the skin becomes cloudy when applied a lot.

On the other hand, organic blocking agents are very diverse, unlike inorganic blocking agents, but bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), Butyl Methoxydibenzoylmethane, Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and disodium phenyl dibenzimidazole tetrasulfonate (DPDT) are mainly used. Among them, DHHB represented by the following formula is a representative organic blocking agent that blocks UV-A. It was first developed by BASF through European Publication No. 1046391, and is currently marketed under the trade name Uvinul A plus.

BASF introduces a method for preparing DHHB according to the following scheme through International Publication WO 03/097578.

However, in this preparation method, sulfuric acid, a strong acid, is used in the esterification step, and the reaction is performed at a high temperature (105 ~ 110 ℃), and as it generates red impurities in the reaction product, a large amount of It has a problem in that it has to go through several refining processes as well as using a bleaching agent.

Meanwhile, BASF disclosed a method for crystallizing DHHB in International Publication WO 2008/135360. However, the crystallization method disclosed in the above patent is a method to obtain DHHB in solid form by completely dissolving above the melting point (54° C.) of DHHB and then cooling it again below the melting point, and pulverization is essential. Since it is difficult to apply to general mass production facilities, there are restrictions on mass production. Therefore, it is required to develop a DHHB manufacturing method that is easy to manufacture and can be mass-produced commercially.

The present invention relates to a method for producing diethylaminohydroxybenzoylhexylbenzoate, which can improve the existing production method, which is difficult to decolorize, by generating a large amount of red impurities by reacting with a strong acid, and diethylaminohydroxybenzoylhexyl produced thereby We would like to provide benzoate.

In addition, the present invention provides a method for producing diethylaminohydroxybenzoylhexylbenzoate, which can be produced economically with high yield by reducing the number of purifications while using a small amount of decolorizing agent, and diethylaminohydroxybenzoylhexyl prepared thereby We would like to provide benzoate.

The present invention relates to a diethylamino comprising the step of preparing a compound represented by the following formula (1) by reacting a compound represented by the following formula (III) with N,N-diethylamino-hydroxybenzoyl-benzoic acid represented by the following formula (II) A method for preparing hydroxybenzoylhexylbenzoate is provided.

According to the production method of the present invention, it is possible to improve the existing method for producing diethylaminohydroxybenzoylhexylbenzoate, which is difficult to decolorize by reacting in a strong acid to generate a large amount of red impurities. Specifically, the present invention can reduce the number of purifications while using a small amount of decolorizing agent, so that diethylaminohydroxybenzoylhexylbenzoate can be produced in high yield and mass-produced economically. , it is possible to improve the existing method for producing diethylaminohydroxybenzoylhexylbenzoate, which is difficult to discolor because it reacts in strong acid to generate a large amount of red impurities. Specifically, the present invention can reduce the number of purifications while using a small amount of decolorizing agent, so that diethylaminohydroxybenzoylhexylbenzoate can be manufactured in high yield and economically mass-produced.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily carry out the present invention. The embodiments of the present invention are provided in order to more completely explain the present invention to those of ordinary skill in the art. Accordingly, the embodiment of the present invention may be modified in various other forms, and the scope of the present invention is not limited to the embodiments described below.

Throughout the specification of the present invention, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.

Throughout the specification of the present invention, when a step is located “on” or “before” another step, this means not only a case in which a step is in a direct time-series relationship with another step, but also a step of mixing after each step and Likewise, the order of two steps may include the same rights as in the case of an indirect time-series relationship in which the time-series order may change.

The terms "about", "substantially", etc. to the extent used throughout the specification of the present invention are used in or close to the numerical value when the manufacturing and material tolerances inherent in the stated meaning are presented, and the present invention It is used to prevent an unconscionable infringer from using the disclosure in which exact or absolute figures are mentioned to help the understanding of the As used throughout this specification, the term “step of” or “step of” does not mean “step for.”

The present invention includes the step of preparing a compound represented by the following formula (1) by reacting a compound represented by the following formula (III) with N,N-diethylamino-hydroxybenzoyl-benzoic acid represented by the following formula (II), diethyl A process for the preparation of aminohydroxybenzoylhexylbenzoate is provided:

[Formula I]

[Formula II]

[Formula III]

L is chloro, bromo, iodo, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexylsulfite or hexylalkylsulfonyl.

According to one embodiment of the present invention, the reaction may be carried out under basic conditions.

Specifically, the base may be an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydroxide and potassium hydroxide. However, the present invention is not limited thereto.

In addition, the base may be an organic base selected from the group consisting of triethylamine, diisopropylethylamine, diethylamine and pyridine. However, the present invention is not limited thereto.

Also, according to one embodiment of the present invention, the compound represented by Formula II may be prepared by reacting 3-diethylaminophenol with phthalic anhydride. However, the present invention is not limited thereto.

Also, according to one embodiment of the present invention, the compound represented by Formula III may be prepared using n-hexanol as a starting material.

According to the present invention, the present invention provides a method for preparing crystalline particles of the compound of Formula 1 below.

The crystallization may be performed using a C1-C4 alcohol as a crystallization solvent. For example, the crystallization may be methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol or t-butanol.

Specifically, the crystallization manufacturing method may include the following steps:

1) adding the crystallization solvent to the concentrated residue of diethylaminohydroxybenzoylhexylbenzoate represented by Formula I;

2) dissolving by raising the internal temperature to 30 ~ 50 ℃;

3) after confirming complete dissolution, slowly cooling at a rate of 2 to 4 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C;

4) Slow cooling at a rate of 2 to 4 °C/hr to 0 to 5 °C to prepare crystalline particles.

According to the production method of the present invention mentioned above, it is possible to improve the existing method for producing diethylaminohydroxybenzoylhexylbenzoate, which is difficult to decolorize by reacting in a strong acid to generate a large amount of red impurities. Specifically, the present invention can reduce the number of purifications while using a small amount of decolorizing agent, so that diethylaminohydroxybenzoylhexylbenzoate can be manufactured in high yield and economically mass-produced.

In addition, the present invention provides diethylaminohydroxybenzoylhexylbenzoate crystalline particles prepared according to the production method of the present invention.

The crystalline particles of diethylaminohydroxybenzoylhexylbenzoate of the present invention are obtained in a crystalline form by being obtained according to the production method of the present invention, and thus have the advantage that they can be used without pulverization.

The crystalline particles of diethylaminohydroxybenzoylhexylbenzoate prepared according to the method of the present invention may have an average particle size of 1 μm to 500 μm. Specifically, the average particle size is 10 μm to 100 μm.

In addition, the crystalline particles of diethylaminohydroxybenzoylhexylbenzoate prepared according to the production method of the present invention have a bulk density exceeding 0.28 g/ml.

In addition, the crystalline particles of diethylaminohydroxybenzoylhexylbenzoate prepared according to the production method of the present invention have a purity of 98% by weight or more.

Example

Hereinafter, the present invention will be described in detail by way of preparation examples and examples. However, the following Preparation Examples or Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Preparation Examples or Examples.

Preparation Example 1. Synthesis of 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid

3-diethylaminophenol (1.0 kg, 7.87 mol) and phthalic anhydride (1.17 kg, 7.87 mol) were placed in a 3-neck flask and stirred with toluene (5.0 L). The temperature inside the reactor was raised to 110 ~ 115 ℃, stirred for 2 hours, cooled to 0 ~ 10 ℃, the precipitated solid was filtered to obtain the title compound (1.7 kg, 89.9%).

¹ H NMR (CDCl ₃ ): 12.52 (s, 1H), 7.91 (dd, 1H), 7.62 (m, 2H), 7.33 (dd, 1H), 6.74 (d, 1H), 6.13 (dd, 1H), 6.20 (d, 1H), 1.16 (m, 6H)

Preparation Example 2-1. Synthesis of 1-chlorohexane

1-hexanol (1.2 kg, 11.70 mol) and DMF (8.5 g, 0.12 mol) were stirred, and SOCl ₂ (2.1 kg, 17.6 mol) was added dropwise while maintaining an internal temperature of 30° C. or less. After completion of the dropwise addition, the internal temperature was raised to 80 ~ 90 ℃ and stirred for 5 hours. After confirming the completion of the reaction, 5 L of purified water was added after cooling, and the layers were separated to obtain the title compound (1.3 kg, 94.2 %).

¹ H NMR (CDCl ₃ ): 3.49 (t, 2H), 1.72 (m, 2H), 1.28 (m, 2H), 1.27 (m, 4H), 0.88 (m, 3H).

Preparation Example 2-2. Synthesis of 1-bromohexane

1-hexanol (1.2 kg, 11.70 mol) and THF (6.0 L) were stirred, and PBr ₃ (3.2 kg, 17.6 mol) was added dropwise while maintaining an internal temperature of 10° C. or less. After completion of the dropwise addition, the internal temperature was maintained at 10° C. or lower and stirred for 3 hours. After confirming the completion of the reaction, 5 L of purified water was added, and the layers were separated to obtain the title compound (1.8 kg, 91.4 %).

¹ H NMR (CDCl ₃ ): 3.40 (t, 2H), 1.85 (m, 2H), 1.43 (m, 2H), 1.31 (m, 4H), 0.90 (m, 3H).

Preparation 2-3. Synthesis of hexyl methanesulfonate

1-hexanol (1.2 kg, 11.70 mol), triethylamine (2.4 kg, 23.40 mol), and methylene chloride (12.0 L) were stirred, and MsCl (1.6 kg, 14.0 mol) was added while maintaining the internal temperature of 10 ° C or less. was added dropwise. After completion of the dropwise addition, the internal temperature was maintained at 10° C. or lower and stirred for 3 hours. After adding 5 L of purified water to layer separation, the separated organic layer was concentrated under reduced pressure to obtain the title compound (1.9 kg, 88.1 %).

¹ H NMR (CDCl ₃ ): 4.23 (t, 2H), 3.00 (s, 3H), 1.75 (m, 2H), 1.40 (m, 3H), 1.32 (m, 3H), 0.90 (m, 3H).

Preparation Example 2-4. Synthesis of hexyl 4-methylbenzenesulfonate

1-hexanol (1.2 kg, 11.70 mol), TsCl (2.7 kg, 14.0 mol), and methylene chloride (12.0 L) were stirred, and triethylamine (2.4 kg, 23.40 mol) was added while maintaining the internal temperature of 10 ° C or less. was added dropwise. After completion of the dropwise addition, the internal temperature was maintained at 10° C. or lower and stirred for 6 hours. 5 L of purified water was added, the layers were separated, and the separated organic layer was concentrated under reduced pressure to obtain the title compound (2.8 kg, 93.2 %).

¹ H NMR (CDCl ₃ ): 7.78 (m, 2H), 7.34 (m, 2H), 4.02 (m, 2H), 2.45 (s, 3H), 1.65 (m, 2H), 1.47-1.04 (m, 6H) ), 0.85 (m, 3H).

Preparation Example 2-5. Synthesis of dihexylsulfite

1-hexanol (1.2 kg, 11.70 mol) and DMF (8.5 g, 0.12 mol) were stirred, and SOCl ₂ (0.7 kg, 5.9 mol) was added dropwise while maintaining an internal temperature of 30° C. or less. After completion of the dropwise addition, the internal temperature was raised to 30 ~ 40 ℃ and stirred for 8 hours. After confirming the completion of the reaction, 5 L of purified water was added after cooling, and the layers were separated to obtain the title compound (1.3 kg, 90.0 %).

¹ H NMR (CDCl ₃ ): 3.95 (m, 4H), 1.63 (m, 4H), 1.27 (m, 6H), 0.86 (m, 12H).

Preparation Example 2-6. Synthesis of dihexyl sulfate

1-hexanol (1.2 kg, 11.70 mol) and DMF (8.5 g, 0.12 mol) were stirred, and SO ₂ Cl ₂ (0.8 kg, 5.9 mol) was added dropwise while maintaining an internal temperature of 30° C. or less. After completion of the dropwise addition, the internal temperature was raised to 30 ~ 40 ℃ and stirred for 8 hours. After confirming the completion of the reaction, 5 L of purified water was added after cooling, and the layers were separated to obtain the title compound (1.4 kg, 87.0%).

¹ H NMR (CDCl ₃ ): 4.00 (m, 4H), 1.69 (m, 4H), 1.30 (m, 6H), 0.90 (m, 12H).

Example 1: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

Step 1: Preparation of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, 1-chlorohexane synthesized in Preparation Example 2-1 (0.5 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) was stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 ℃, stirred for 4 hours, cooled, and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 to 50 °C for 1 hour, and then concentrated under reduced pressure.

Step 2

To the concentrated residue obtained in step 1, 4 v/w of methanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid was added, and then the temperature was raised to an internal temperature of 30 to 50 °C to dissolve clearly. After confirming complete dissolution, it was slowly cooled at a rate of 3 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C. When the target temperature is reached, the temperature is maintained and stirred for 1 hour, then slowly cooled at a rate of 3 ℃/hr to 0 ~ 5 ℃. When the target temperature was reached, the temperature was maintained, stirred for 1 hour, and filtered to obtain the title compound (1.2 kg, 86.0%) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 80.3 μm;

Bulk density: 0.34 g/ml;

Purity 99.4%.

Example 2: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

To the concentrated residue obtained in step 1 of Example 1, 4 v/w of ethanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid was added, and the internal temperature was raised to 30-50 ° C. Clearly dissolved. After confirming complete dissolution, it was slowly cooled at a rate of 3 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C. When the target temperature is reached, the temperature is maintained and stirred for 1 hour, then slowly cooled at a rate of 3 ℃/hr to 0 ~ 5 ℃. When the target temperature was reached, the temperature was maintained, stirred for 1 hour, and filtered to obtain the title compound (1.1 kg, 80.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 73.7 μm;

Bulk Density: 0.32 g/ml

Purity 99.6%.

Example 3: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

After adding 4 v/w isopropanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained in step 1 of Example 1, the internal temperature was raised to 30-50 ° C. Clearly dissolved. After confirming complete dissolution, it was slowly cooled at a rate of 3 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C. When the target temperature is reached, the temperature is maintained and stirred for 1 hour, then slowly cooled at a rate of 3 ℃/hr to 0 ~ 5 ℃. When the target temperature was reached, the temperature was maintained, stirred for 1 hour, and filtered to obtain the title compound (1.10 kg, 80.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

Average particle size: 91.2 μm

Bulk density: 0.38 g/ml;

Purity 99.2%.

Example 4: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

After adding 4-v/w 2-butanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained in step 1 of Example 1, the internal temperature was increased to 30 ~ 50 ℃ The temperature was raised to clear dissolution. After confirming complete dissolution, it was slowly cooled at a rate of 3 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C. When the target temperature is reached, the temperature is maintained and stirred for 1 hour, then slowly cooled at a rate of 3 ℃/hr to 0 ~ 5 ℃. When the target temperature was reached, the temperature was maintained, stirred for 1 hour, and filtered to obtain the title compound (1.00 kg, 75.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 12.0 μm;

Bulk density: 0.28 g/ml;

Purity 99.5%.

Example 5: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, 1-bromohexane synthesized in Preparation Example 2-2 (0.7 kg , 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) was stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 ℃, stirred for 4 hours, cooled, and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 to 50 °C for 1 hour, and then concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.90 kg, 65.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 69.4 μm;

Bulk density: 0.32 g/ml;

Purity 99.4%.

Example 6: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, hexyl methanesulfonate synthesized in Preparation Example 2-3 (0.8 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) was stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 ℃, stirred for 4 hours, cooled and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 ~ 50 °C for 1 hour, and then concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.73 kg, 52.4 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 25.8 μm;

Bulk density: 0.30 g/ml;

Purity 99.8%.

Example 7: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, hexyl 4-methylbenzenesulfonate synthesized in Preparation Example 2-4 ( 1.1 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) were stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 ℃, stirred for 4 hours, cooled and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 to 50 °C for 1 hour and then concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.66 kg, 47.6 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 81.3 μm;

Bulk density: 0.37 g/ml;

Purity 99.5%.

Example 8: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, dihexylsulfite synthesized in Preparation Example 2-5 (1.1 kg, 4.22) mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) was stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 ℃, stirred for 4 hours, cooled and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 to 50 °C for 1 hour and then concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (1.12 kg, 80.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 45.2 μm;

Bulk density: 0.32 g/ml;

Purity 99.1%.

Example 9: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, dihexyl sulfate synthesized in Preparation Example 2-6 (1.2 kg, 4.22) mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) was stirred with 1.65 L of DMF. The internal temperature was raised to 100 ~ 110 °C, stirred for 4 hours, cooled, and extracted using 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized using 5% charcoal at an internal temperature of 30 to 50 °C for 1 hour and then concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (1.09 kg, 78.0 %) in the form of crystalline particles.

¹ H NMR (CDCl ₃ ): 12.59 (s, 1H), 8.04 (dd, 1H), 7.55 (m, 2H), 7.34 (dd, 1H), 6.87 (d, 1H), 6.12 (d, 1H), 6.02 (dd, 1H), 4.10 (t, 2H), 3.35 (q, 4H), 1.45 (m, 2H), 1.16 (m, 12H), 0.82 (t, 3H);

average particle size: 82.0 μm;

Bulk density: 0.39 g/ml;

Purity 99.4%.

As confirmed in the Examples, diethylaminohydroxybenzoylhexylbenzoate can be obtained in a high yield according to the manufacturing method of the present invention, and since the decolorization and purification processes can be simplified, mass production is economically possible.

The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and likewise components described as distributed may be implemented in a combined form.

The scope of the present invention is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts are interpreted as being included in the scope of the present invention. should be

Claims (4)

1) adding a crystallization solvent to the concentrated residue of diethylaminohydroxybenzoylhexylbenzoate represented by the following formula (I);
2) dissolving by raising the internal temperature to 30 ~ 50 ℃;
3) after confirming complete dissolution, slowly cooling at a rate of 2 to 4 °C/hr to slowly precipitate crystals, followed by slow cooling to an internal temperature of 15 to 20 °C;
4) crystalline particles of diethylaminohydroxybenzoylhexylbenzoate represented by the following formula (I), comprising the step of producing crystalline particles by cooling to 0 to 5 °C by slow cooling at a rate of 2 to 4 °C/hr manufacturing method.
[Formula 1]

The method of claim 1,
The crystallization solvent is methanol, ethanol, isopropanol, 1-propanol, 1-butanol, 2-butanol, t-butanol, and a method for producing crystalline particles using one selected from the group consisting of mixtures thereof.
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