KR102179649B1 - A preparing method of diethylamino hydroxybenzoyl hexylbenzoate - Google Patents

Abstract

The present invention relates to a method for preparing diethylaminohydroxybenzoylhexylbenzoate, specifically, a method for preparing diethylaminohydroxybenzoylhexylbenzoate, which is easy to manufacture and can be mass-produced commercially, and the diethylaminohydroxybenzoylhexylbenzoate prepared thereby. It relates to ethylaminohydroxybenzoylhexylbenzoate 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

Preparation method of diethylamino hydroxybenzoyl hexylbenzoate {A preparing method of diethylamino hydroxybenzoyl hexylbenzoate}

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

All ultraviolet rays, including ultraviolet rays contained in sunlight, are carcinogens. IARC, an international cancer research institute, classifies all types of ultraviolet rays as group 1 carcinogens, that is, substances that have been confirmed to cause cancer.

In addition to carcinogenicity, ultraviolet rays damage the skin, eyes and immune system and cause skin aging. Theoretically, aging is delayed 27 times without UV light. In particular, UV-B (320 nm ~ 280 nm), which is heavily contained in sunlight, causes burns, and UV-C (280 nm ~ 100 nm), which is used for ultraviolet sterilization, has high energy, so UV-A (400 nm ~ 320 nm) or It is more harmful than UV-B. In addition, UV-A, which was known to be harmless in the past, also has high energy, so it has been found that DNA damage through free radicals is possible. Burning of the skin when exposed to sunlight is a phenomenon that occurs to protect the skin from harmful substances. In addition to damage to health such as skin aging and skin damage, UV rays can also harm cosmetically, such as creating freckles and spots.

As above, UV rays are considered the main cause of various aging and wrinkles, and sunscreens are recommended for all ages. Sunscreen agents are divided into physical blockers and chemical blockers, physical blockers are mainly inorganic compounds that reflect ultraviolet rays (inorganic blockers), and chemical blockers are compositions that release ultraviolet energy by converting it into heat. (Organic blocker).

Inorganic blocking agents are mainly titanium dioxide (titanium dioxide) and zinc oxide. The blocking effect is excellent, but the application is stiff, and if applied a lot, there is a problem that the skin becomes flat and cloudy.

On the other hand, organic blockers have very diverse types, unlike inorganic blockers, 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 brand name Uvinul A plus.

BASF introduces a method of preparing DHHB by the following reaction scheme through International Publication WO 03/097578.

However, this manufacturing method uses sulfuric acid, which is a strong acid in the esterification step, and must be reacted at a high temperature (105 ~ 110 ℃), and a large amount of red color impurities are generated in the reaction product. There is a problem that not only a bleaching agent must be used, but also several purification processes must be performed.

On the other hand, BASF has disclosed a method of crystallizing DHHB in International Publication WO 2008/135360. However, the crystallization method disclosed in the above patent is a method of obtaining DHHB in a solid form by completely dissolving above the melting point (54°C) of DHHB and then cooling it below the melting point, and grinding is essential. Since this is difficult to apply to general mass production facilities, mass production is limited. Therefore, it is required to develop a DHHB manufacturing method that is easy to manufacture and can be mass-produced commercially.

The present invention is a method for preparing diethylaminohydroxybenzoylhexylbenzoate that can improve the existing manufacturing method that is difficult to decolor by generating a large amount of red impurities by reacting in a strong acid, and diethylaminohydroxybenzoylhexyl prepared thereby. To provide benzoate.

In addition, the present invention can reduce the number of purification while using a small amount of bleaching agent, and thus a method for producing diethylaminohydroxybenzoylhexylbenzoate that can be produced economically with high yield, and diethylaminohydroxybenzoylhexyl prepared thereby To provide benzoate.

The present invention is 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. It provides a method for producing hydroxybenzoylhexylbenzoate.

[Formula I]

[Formula II]

[Formula III]

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

In addition, the present invention provides a method for producing crystalline particles of diethylaminohydroxybenzoylhexylbenzoate.

In addition, the present invention provides diethylaminohydroxybenzoylhexylbenzoate prepared by the above preparation method.

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 and generating a large amount of red impurities. Specifically, in the present invention, diethylaminohydroxybenzoylhexylbenzoate can be prepared in high yield by reducing the number of purifications while using a small amount of the bleaching agent, 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 be easily carried out. 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, embodiments of the present invention may be modified into 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 positioned "on" or "before" another step, it is not only the case that a step is in a direct time series relationship with another step, but also the mixing step after each step and Likewise, the order of the two steps may contain the same rights as in the case of an indirect time-series relationship that can change the order of the time series.

The terms "about", "substantially", etc. of the degree used throughout the specification of the present invention are used at or close to the numerical value when manufacturing and material tolerances specific to the stated meaning are presented, and the present invention To aid in understanding of, accurate or absolute figures are used to prevent unreasonable use of the stated disclosure by unscrupulous infringers. As used throughout the specification of the present application, the term "step (to)" or "step of" does not mean "step for".

The present invention comprises 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 method for preparing aminohydroxybenzoylhexylbenzoate is provided:

[Formula I]

[Formula II]

[Formula III]

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

According to an 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, it 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, it is not limited thereto.

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

In addition, according to an 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 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, slow cooling at a rate of 2 to 4°C/hr to slowly precipitate crystals and slow cooling to an internal temperature of 15 to 20°C;

4) Slow cooling at a rate of 2 to 4°C/hr and cooling to 0 to 5°C to produce 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, in the present invention, diethylaminohydroxybenzoylhexylbenzoate can be prepared in high yield by reducing the number of purifications while using a small amount of the bleaching agent, and economically mass-produced.

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

The diethylaminohydroxybenzoylhexylbenzoate crystalline particles 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 as they are without grinding.

Diethylaminohydroxybenzoylhexylbenzoate crystalline particles prepared according to the preparation 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.

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

Further, the diethylaminohydroxybenzoylhexylbenzoate crystalline particles 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 manufacturing examples and examples. However, the following Preparation Examples or Examples are merely illustrative of the present invention, and the contents of the present invention are 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 internal temperature of the reactor was raised to 110 to 115 °C, stirred for 2 hours, cooled to 0 to 10 °C, and 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 the dropwise addition was completed, the internal temperature was raised to 80 ~ 90 ℃ and stirred for 5 hours. After confirmation of completion of the reaction, the mixture was cooled, 5 L of purified water was added, 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 the dropwise addition was completed, the internal temperature was maintained at 10° C. or less 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 Example 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 an internal temperature of 10 ℃ or less. Added dropwise. After the dropwise addition was completed, the internal temperature was maintained at 10° C. or less and stirred for 3 hours. After layer separation by adding 5 L of purified water, 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 an internal temperature of 10 °C or less. Added dropwise. After the dropwise addition was completed, the internal temperature was maintained at 10° C. or less and stirred for 6 hours. After layer separation by adding 5 L of purified water, 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 the dropwise addition was completed, the internal temperature was raised to 30 ~ 40 ℃ and stirred for 8 hours. After confirming the completion of the reaction, the mixture was cooled, 5 L of purified water was added, 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 the dropwise addition was completed, the internal temperature was raised to 30 ~ 40 ℃ and stirred for 8 hours. After confirmation of completion of the reaction, the mixture was cooled, 5 L of purified water was added, 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 synthesized in Preparation Example 1 (1.1 kg, 3.51 mol), 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 °C, stirred for 4 hours, cooled, and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized for 1 hour using 5% charcoal at an internal temperature of 30 to 50° C., 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 the internal temperature was raised to 30 to 50° C. to clear dissolution. After confirming complete dissolution, slow cooling was performed 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°C/hr and cooled to 0 ~ 5°C. 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;

99.4% purity.

Example 2: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

After adding 4 v/w of ethanol to the concentrated residue obtained in step 1 of Example 1 compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid, the internal temperature was raised to 30 to 50°C. Clearly dissolved. After confirming complete dissolution, slow cooling was performed 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°C/hr and cooled to 0 ~ 5°C. 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

99.6% purity.

Example 3: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

After adding 4 v/w of 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 to 50°C. Clearly dissolved. After confirming complete dissolution, slow cooling was performed 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°C/hr and cooled to 0 ~ 5°C. 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;

99.2% purity.

Example 4: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

After adding 4 v/w of 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 30 to 50°C. The temperature was raised to clear dissolution. After confirming complete dissolution, slow cooling was performed 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°C/hr and cooled to 0 ~ 5°C. 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;

99.5% purity.

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 (0.7 kg) synthesized in Preparation Example 2-2 , 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 for 1 hour using 5% charcoal at an internal temperature of 30 to 50°C, 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;

99.4% purity.

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 °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 for 1 hour using 5% charcoal at an internal temperature of 30 to 50° C., 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;

99.8% purity.

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) 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 for 1 hour using 5% charcoal at an internal temperature of 30 to 50°C, 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;

99.5% purity.

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 °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 for 1 hour using 5% charcoal at an internal temperature of 30 to 50°C, 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;

99.1% purity.

Example 9: Synthesis of diethylaminohydroxybenzoylhexylbenzoate

2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid synthesized in Preparation Example 1 (1.1 kg, 3.51 mol), 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 for 1 hour using 5% charcoal at an internal temperature of 30 to 50°C, 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;

99.4% purity.

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

The above description of the present invention is for illustrative purposes only, and those of ordinary skill in the technical field to which the present invention pertains will be able to understand that it is possible to easily transform it 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 limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as being distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the claims to be described later rather than the detailed description, and it is interpreted that the meaning and scope of the claims, and all changes or modified forms derived from the concept of equivalents thereof are included in the scope of the present invention. Should be.

Claims (8)

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,
Method for preparing diethylaminohydroxybenzoylhexylbenzoate:
[Formula I]

[Formula II]

[Formula III]

L is chloro, broro, iodo, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexylsulfite or hexylalkylsulfonyl.
The method of claim 1,
The reaction is to be carried out under basic conditions.
The method of claim 2,
The base is an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydroxide and potassium hydroxide.
The method of claim 2,
The base is an organic base selected from the group consisting of triethylamine, diisopropylethylamine, diethylamine, and pyridine.
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