ÉSTER HEXÍLICO DE ÁCIDO 2-(4'-DIETILAMINO-2'-HIDROXIBENZOIL)BENZOICO

Description

34 2-(4'-DIETHYLAMINO-2'HYDROXYBENZOYL)BENZOIC ACID HEXYL ESTER (Divided from BR 11 2022 016712 1) Description

[001] The present invention relates to a process for isolating high-purity 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a low content of phthalic acid dialkyl ester.

[002] UV radiation causes harmful effects on human skin. In addition to the acute effect of sunburn on the skin, UV radiation is also known to increase the risk of skin cancer. Furthermore, prolonged exposure to UV-A and UV-B light can cause phototoxic and photoallergenic reactions in the skin and can accelerate skin aging.

[003] To protect human skin from UV radiation, there are various UV sunscreen filters (also known as UV absorbers), including UV-A filters, UV-B filters, and broadband filters. These filters are added to sunscreens or cosmetic compositions. UV filters are organic or inorganic compounds, particulate or non-particulate, all with high absorption efficacy in the UV light range. In general, UV light can be divided into UV-A radiation (320 - 400 nm) and UV-B radiation (280 - 320 nm). Depending on the position of the absorption maxima, UV filters are divided into UV-A and UV-B filters. If a UV filter absorbs both UVA and UV-B light, it is called a broadband absorber.

[004] Since 2006, the EU commission has recommended that all sunscreens or cosmetic compositions should have a UV-A protection factor, which is at least one third of the labeled sun protection factor (SPF), where the sun protection factor refers primarily to the UV-B protection factor.

[005] The hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is an effective UV-A filter and is used to protect the skin. Petition 870260057225, dated 12 / 06 / 2026, page 13 / 56 2 / 34 of UV radiation (e.g., in sunscreen). The hexyl ester of 2(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is represented below, and will hereinafter also be referred to as compound of formula (I). (I)

[006] The manufacturing processes for hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid are known from, for example, DE 10011317, EP2155660 and WO 2003097578. In this regard, several challenges have been observed.

[007] During synthesis, the byproduct dihexyl ester of italic acid (also known as PSDHE, dihexyl phthalate) is formed. The final product may still contain up to 50-150 ppm of PSDHE. According to recent findings, the PSDHE content should be as low as possible, since this substance can, according to the Harmonised Classification and Labelling (ATP05), impair fertility and harm the fetus.

[008] Furthermore, during the synthesis of the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester process, type B dyes (e.g., [9-(2-carboxyphenyl)-6-diethylamino-3-xanthenylidene]diethylammonium salts) and corresponding esters are formed as impurities, leading to undesirable discoloration of the final product. To purify the final product (less than 10 ppm of Rhodamine B type dyes), an additional purification step is required. So far, the purification step comprises dissolving the contaminated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in a non-polar solvent such as cyclohexane or toluene, adsorbing onto a bed of activated carbon or silicic acid, and evaporating the solvent after passing through the bed.

[009] After the subsequent isolation of the hexyl ester of 2-(4' Petition 870260057225, dated 12 / 06 / 2026, page 14 / 56 / 34 diethylamino-2'-hydroxybenzoyl)benzoic acid by separating toluene and / or 1-hexanol by distillation, the clean final product is bottled as a melt. Once the product is bottled as a melt and the first crystal growth occurs after storage for about six weeks at room temperature, the user must heat the entire package to a temperature above the melting point of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in order to remove the liquid product from the packaging.In order to provide a crystalline end product that is safe and easy to handle, the following additional processing steps are necessary: ​​a) providing a clear melt of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester at a temperature above 57°C, b) crystallizing the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester at a temperature below 57°C, and c) fragmenting the crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester to the desired particle size.

[0010] Therefore, there is a continuing need for a rapid and efficient purification process of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester. In this respect, it has been an objective of the present invention to provide an optimized process for isolating crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester. It has been especially an objective to provide a process for isolating crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in which the amount of phthalic acid dihexyl ester is reduced. Furthermore, it has been an objective of the present invention to provide a process for isolating crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in which the amount of colored impurities is reduced.Finally, it has been an objective of the present invention to provide a rapid process for isolating the crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, which additionally provides a safe and convenient end product to handle. Petition 870260057225, dated 12 / 06 / 2026, page 15 / 56 / 34

[0011] Surprisingly, it has been found that at least one of the above objectives can be achieved by the process according to the present invention. The inventive process provides 2-(4'-diethylamino2'-hydroxybenzoyl)benzoic acid hexyl ester with low PSDHE content (less than 15 ppm) and low content of colored impurities such as free-flowing crystals.

[0012] In particular, the inventors of the present invention have discovered a process for effectively purifying the compound of formula (I).

[0013] The present invention, therefore, relates, in a first aspect, to a process for isolating the crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester comprising the steps of a) Dissolve a mixture comprising hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid in a solvent with a boiling point of no more than 110°C to obtain a solution; b) cool the solution to a temperature in the range of 20 to 40°C; c) optionally add 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals to the solution; d) cool the solution to a temperature below 5°C to obtain a suspension; e) Filter the suspension to isolate the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid in crystalline form.

[0014] Next, the preferred modalities of the first aspect process are described in more detail. It should be understood that each preferred modality is relevant on its own, as well as in combination with other preferred modalities.

[0015] In a preferred embodiment A1 of the first aspect, the mixture in step a) comprises at least 85% by weight of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester and up to 15% of impurities including solvent residues of solvents with a boiling point above 110°C and dialkyl esters of phthalic acid, wherein the amounts Petition 870260057225, dated 12 / 06 / 2026, p. 16 / 56 / 34 of % by weight are, in each case, based on the total weight of the mixture.

[0016] In a preferred embodiment A2 of the first aspect, impurities include 1-hexanol in an amount of up to 14% by weight based on the total weight of the mixture and dialkyl esters of phthalic acid in an amount of 50 to 200 ppm.

[0017] In a preferred embodiment A3 of the first aspect, the solvent in step a) has a boiling point of at most 85°C.

[0018] In a preferred embodiment A4 of the first aspect, the solvent in step a) is polar and / or is selected from methanol, ethanol, 1-propanol and isopropanol.

[0019] In a preferred embodiment A5 of the first aspect, in step a), the mixture is dissolved at a temperature of 45 to 55°C.

[0020] In a preferred embodiment A6 of the first aspect, in step b), the solution is cooled to a temperature of 25 to 30°C for a period of at least 10 minutes.

[0021] In a preferred embodiment A7 of the first aspect, in step d), the solution is cooled to a temperature below -5°C for a period of at least 3 hours, preferably at least 5 hours.

[0022] In a preferred embodiment A8 of the first aspect, cooling is carried out by means of a linear or non-linear cooling rate.

[0023] In a preferred embodiment A9 of the first aspect, step d) further comprises stirring the resulting suspension at a temperature below 0°C for at least 3 hours, preferably at least 6 hours.

[0024] In a preferred embodiment A10 of the first aspect, the process further comprises the step of f) Wash the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a solvent, optionally an aqueous base, optionally a surfactant, and optionally water. Petition 870260057225, dated 12 / 06 / 2026, p. 17 / 56 / 34

[0025] In a preferred embodiment A11 of the first aspect, the solvent in the washing step f) is the solvent used in step a) of the process.

[0026] In a preferred embodiment A12 of the first aspect, the aqueous base in the washing step f) is present and is a solution of potassium or sodium carbonate, a solution of potassium or sodium bicarbonate, a solution of potassium or sodium hydroxide, or an aqueous solution of ammonia.

[0027] In a preferred embodiment A13 of the first aspect, the surfactant in the washing step f) is present and is selected from the group consisting of alkylbenzyl sulfonate, sodium lauryl sulfate, ammonium lauryl sulfate, disodium lauryl sulfosuccinate, cocoamphocarboxyglycinate, decyl polyglucoside, cetearyl alcohol, stearyl alcohol, cocamidopropyl betaine, decyl glucoside, glyceryl cocoate, sodium cocoyl isethionate, almond glycerides, sodium lauryl sulfoacetate, sodium lauroyl sarcosinate, sodium methyl cocoyl taurate, sucrose cocoate, polysorbate 20 and polysorbate 80, preferably sodium salt of dodecylbenzene sulfonic acid.

[0028] In a preferred embodiment A14 of the first aspect, the process additionally comprises the step of g) drying the isolated 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid hexyl ester.

[0029] In yet another preferred embodiment A15 of the first aspect, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester alone has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a 1-hexanol content of less than 200 ppm, a Gardner value of 8.3 or less and a rhodamine content of less than 1 ppm. Petition 870260057225, dated 12 / 06 / 2026, p. 18 / 56 / 34

[0030] In a second aspect, the present invention relates to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm, and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine content of less than 1 ppm. DETAILED DESCRIPTION

[0031] Before describing in detail exemplary embodiments of the present invention, important definitions are provided for the understanding of the present invention.

[0032] As used in this descriptive report and the appended claims, the singular forms of “a” and “an” also include their respective plurals, unless the context clearly indicates otherwise. In the context of the present invention, the terms “about” and “approximately” denote a range of precision that one skilled in the art will understand to still ensure the technical effect of the feature in question. The term typically indicates a deviation from the stated numerical value of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5%. It should be understood that the term “comprising” is not limiting. For the purposes of the present invention, the term “consisting of” is considered to be a preferred embodiment of the term “comprising in”. If in the following parts a group is defined as comprising at least a certain number of embodiments, this group should also encompass one that preferably consists only of those embodiments.Furthermore, the terms “first”, “second”, “third” or “(a)”, “(b)”, “(c)”, “(d)”, etc. and the like, in description and claims, are used to distinguish between. Petition 870260057225, dated 12 / 06 / 2026, p. 19 / 56 / 34 similar elements and not necessarily to describe a sequential or chronological order. It should be understood that the terms then used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in sequences different from those described or illustrated herein. In the case of the terms “first”, “second”, “third” or “(a)”, “(b)”, “(c)”, “(d)”, “i”, “ii” etc. referring to the steps of a method or use or trial, there is no coherence of time or time interval between the steps, i.e., the steps may be performed simultaneously or there may be time intervals of seconds, minutes, hours, days, weeks, months or even years between these steps, unless otherwise indicated in the application as set forth above or below. It should be understood that this invention is not limited to methodology, protocols, reagents, etc.The specific details described herein may vary. It should also be understood that the terminology used in this document is only for the purpose of describing particular embodiments and is not intended to limit the scope of the present invention, which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used in this document have the same meanings commonly understood by a person skilled in the art.

[0033] The term “compound according to the invention” or “compound of formula (I)” refers to 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid hexyl ester.

[0034] The term “halogen” denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

[0035] The term “alkyl”, as used herein, denotes in each case a straight or branched chain alkyl group normally having from 1 to 20 carbon atoms, preferably from 2 to 18 carbon atoms, more preferably from 4 to 12 carbon atoms. Examples of an alkyl group are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, Petition 870260057225, of 06 / 12 / 2026, p. 20 / 56 / 34 n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl. Iso-butyl and n-hexyl are preferred in particular n-hexyl.

[0036] The term “(Cn-Cm-alkyl)” as used in this document denotes in each case a linking moiety, wherein the moieties attached to it are attached to the terminal carbons.

[0037] The term “body care product” refers to any product suitable for application to the human body, for example, sunscreen compositions, bath products, preparations containing fragrances and odoriferous substances, hair care products, toothpastes, decorative preparations and cosmetic formulations containing active ingredients. Sunscreen compositions are preferred.

[0038] The term “sunscreen composition” or “sunscreen” or “skin care product” refers to any topical product that reflects and / or absorbs certain portions of UV radiation. Thus, the term “sunscreen composition” should be understood as including not only sunscreen compositions but also any cosmetic compositions that provide UV protection. The term “topical product” refers to a product that is applied to the skin and may refer, for example, to sprays, lotions, creams, oils, foams, powders, or gels. According to the present invention, the sunscreen composition may comprise one or more active agents, for example, organic UV filters, as well as other ingredients or additives, for example, emulsifiers, emollients, viscosity regulators, stabilizers, preservatives, or fragrances.

[0039] The term “daily care composition” refers to any topical product that reflects or absorbs certain portions of UV radiation and is used as a daily care product for the human body, for example, for the face, body, or hair. A daily care composition may comprise Petition 870260057225, dated 12 / 06 / 2026, page 21 / 56 / 34 one or more active agents, for example, organic or inorganic UV filters, as well as other ingredients or additives, for example, emulsifiers, emollients, viscosity regulators, stabilizers, preservatives or fragrances.

[0040] Suitable bath and shower additives include, for example, shower gels, bath salts, bubble baths and soaps.

[0041] Suitable preparations containing fragrances and odoriferous substances are, in particular, aromas, perfumes, toilet waters and shaving lotions (aftershave preparations).

[0042] Suitable hair products include, for example, shampoos for humans and animals, particularly dogs, hair conditioners, hair styling and treatment products, permanent wave agents, hair sprays and lacquers, hair gels, hair fixatives and hair dyeing or bleaching agents.

[0043] Suitable toothpastes include, for example, toothpaste, mouthwash, anti-plaque preparations and denture cleaning agents.

[0044] Suitable decorative preparations include, for example, lipsticks, nail polishes, eye shadows, mascara, dry and wet makeup, blush, powders, depilatory agents and bronzers.

[0045] Suitable cosmetic formulations containing active ingredients are, for example, hormonal preparations, vitamin preparations, plant extract preparations and antibacterial preparations.

[0046] The body care products mentioned may be in the form of creams, ointments, pastes, foams, gels, lotions, powders, makeup, sprays, sticks or aerosols. They preferably contain the compound of formula (I) in the aqueous phase. Thus, the compound of formula (I) can act as a light stabilizer.

[0047] The term “photostability” refers to the ability of a filter Petition 870260057225, dated 12 / 06 / 2026, p. 22 / 56 / 34 UV radiation, or any other molecule, when exposed to sunlight, means that the compound remains stable after irradiation. In particular, this means that the compound does not undergo a degradation process due to UV radiation.

[0048] The term “critical wavelength” is defined as the wavelength at which the area under the UV protection curve (% protection versus wavelength) represents 90% of the total area under the curve in the UV region (280-400 nm). For example, a critical wavelength of 370 nm indicates that the protection of the sunscreen composition is not limited to UV-B wavelengths, i.e., wavelengths of 280-320 nm, but extends to 370 nm such that 90% of the total area under the protection curve in the UV region is achieved at 370 nm.

[0049] The term “ultraviolet filter” or “UV filter,” as used in this document, refers to organic or inorganic compounds that can absorb and / or reflect UV radiation caused by sunlight. UV filters can be classified based on their UV protection curve as UV-A, UV-B, or broadband filters. In the context of this application, broadband filters can be listed as UV-A filters, as they also provide UV-A protection. In other words, preferred UV-A filters also include broadband filters.

[0050] The definition of “broadband” protection (also called broad-spectrum or wide-spectrum protection) is based on the “critical wavelength”. For broadband coverage, both UV-B and UVA protection must be provided. According to US requirements, a critical wavelength of at least 370 nm is required to achieve broad-spectrum protection. Furthermore, the European Commission recommends that all sunscreens or cosmetic compositions should have a UVA protection factor that is at least one-third of the labeled sun protection factor (SPF), e.g., if the sunscreen composition has an SPF of 30, the UVA protection factor should be at least 10. Petition 870260057225, dated 12 / 06 / 2026, page 23 / 56 / 34

[0051] The preferred embodiments with respect to the process according to the present invention are described below. It should be understood that the preferred embodiments of the invention are preferred alone or in combination with each other.

[0052] As indicated above, the present invention relates, in one embodiment, to a process for isolating crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester comprising the steps of a) dissolving a mixture comprising 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in a solvent having a boiling point of no more than 110°C to obtain a solution; b) cool the solution to a temperature in the range of 20 to 40°C; c) optionally add 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals to the solution; d) cool the solution to a temperature below 5°C to obtain a suspension; e) Filter the suspension to isolate the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid in crystalline form.

[0053] The preferred methods in relation to the process are defined below.

[0054] In a preferred embodiment of the present invention, the mixture applied in step a) is pretreated in vacuum. Preferably, the mixture applied in step a) undergoes a vacuum drying pretreatment at a temperature of 70 to 150°C, more preferably 90 to 140°C, and in particular 100 to 130°C, before dissolving in a solvent with a boiling point of no more than 110°C. Preferably, the pretreatment is carried out at a pressure of 0.01 to 80 kPa (0.1 to 800 mbar), more preferably 0.1 to 70 kPa (1 to 700 mbar), and in particular 0.5 to 60 kPa (5 to 600 mbar). Ideally, pre-treatment is carried out 5 to 360 minutes in advance, more preferably 10 to 250 minutes, and in particular 20 to 120 minutes. Petition 870260057225, dated 12 / 06 / 2026, p. 24 / 56 13 / 34

[0055] In one embodiment of the present invention, the mixture in step a) comprises at least 85%, preferably 90%, by weight of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester and up to 15%, preferably 10%, of impurities including solvent residues of solvents with a boiling point above 110°C and dialkyl esters of italic acid, wherein the % by weight amounts are, in each case, based on the total weight of the mixture.

[0056] In one embodiment of the present invention, the impurities include solvents with a boiling point above 110°C in an amount of up to 14%, preferably up to 12%, more preferably up to 10%, even more preferably up to 9%, and in particular up to 8%, by weight based on the total weight of the mixture and dialkyl esters of phthalic acid in an amount of 50 to 200 ppm, preferably 55 to 150 ppm.

[0057] In this respect, it should be understood that, according to the present invention, dialkyl esters of phthalic acid are defined as having formula (A) o wherein R1 and R2 are C4-C12-alkyl, preferably wherein R1 and R2 are both n-hexyl.

[0058] In a preferred embodiment of the present invention, the impurities include 1-hexanol. In yet another preferred embodiment of the present invention, the impurities include 1-hexanol in an amount of up to 14%, preferably up to 12%, more preferably up to 10%, even more preferably up to 9%, and in particular up to 8%, by weight based on the total weight of the mixture, and dihexyl esters of phthalic acid in an amount of 50 to 200 ppm, preferably 55 to 150 ppm.

[0059] Toluene can also be an impurity according to the Petition 870260057225, dated 12 / 06 / 2026, p. 25 / 56 14 / 34 present invention, which can be understood in the mixture applied in step a) in an amount of up to 10%, preferably up to 5% and in particular up to 3%, by weight based on the total weight of the mixture.

[0060] Furthermore, according to the present invention, it should be understood that the impurities also comprise colored impurities. In particular, Rhodamine B (represented by formula (B)) and Rhodamine B derivatives. The C6 alkyl ester Rhodamine B derivative (represented by formula (C)) may be referred to as a Rhodamine B derivative by way of example.

[0061] In one embodiment of the present invention, the mixture in step a) has a Gardner Value greater than 9.

[0062] In one embodiment of the present invention, the solvent in step a) has a boiling point of at most 100°C, preferably at most 90°C, more preferably at most 85°C, even more preferably at most 83°C, and in particular at most 80°C. In one embodiment of the present invention, the solvent in step a) has a boiling point in the range of 30 to 110°C, preferably 40 to 100°C, more preferably 45 to 90°C, even more preferably 50 to 85°C, and in particular 60 to 85°C.

[0063] In one embodiment of the present invention, the solvent in step a) is polar. It should be understood that a polar solvent has a dielectric constant (ε) of 15 or more, preferably 18 or more. In a preferred embodiment of the present invention, the solvent in step a) has a dielectric constant (ε) of 15 to 100. The polarity may alternatively or additionally be expressed by a dipole moment (μ) of more than 1. Petition 870260057225, dated 12 / 06 / 2026, p. 26 / 56 / 34 preferably more than 2. In one embodiment of the present invention, the solvent in step a) has a dipole moment (μ) of 1 to 10, preferably more than 2 to 10, more preferably 3 to 8. The dipole moment (μ) is indicated as Debye. In a preferred embodiment of the present invention, the solvent in step a) has a dielectric constant (ε) of 15 to 100 and a dipole moment (μ) of 1 to 10.

[0064] In one embodiment of the present invention, the solvent in step a) has low toxicity and is preferably miscible with water. Solvents with low toxicity are, for example, described in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH Harmonised Guideline, Impurities: Guideline for Residual Solvents, Q3C(R6) and Toxicological Data for Class 3 Solvents, Supporting Document Q3C 3. Acetone, isopropyl acetate, methyl acetate, 2-butanol, methyl ethyl ketone, tert-butyl methyl ether, ethanol, ethyl acetate, 1-propanol, ethyl ether, 2-propanol, ethyl formate, propyl acetate, formic acid and trimethylamine may be named as suitable solvents.

[0065] In one embodiment of the present invention, the solvent in step a) is an alcohol, preferably selected from methanol, ethanol, 2-methyl-2-propanol, 1-propanol and isopropanol, which may be further substituted by a halogen (such as to obtain 2,2,2-trifluoromethanol, 2,2,2-trifluoroethanol or 2-fluoroethanol). In a particular embodiment of the present invention, the solvent in step a) is selected from methanol, ethanol, 1-propanol and isopropanol, preferably ethanol. It should be understood that, according to the present invention, the solvent in step a) may be a mixture of the above solvents.

[0066] In one embodiment of the present invention, the mixture in step a) is dissolved at a temperature of at least 30°C, preferably at least 35°C, more preferably at least 40°C, and even more preferably at least 45°C. In a preferred embodiment of Petition 870260057225, dated 12 / 06 / 2026, p. 27 / 56 / 34 present invention, in step a) the mixture is dissolved at a temperature of 35 to 80°C, preferably 40 to 60°C, more preferably 45 to 55°C and, in particular, 48 to 52°C.

[0067] In one embodiment of the present invention, the mixture and the solvent with a boiling point of no more than 110°C in step a) have a ratio of 1:1.5 to 1:3.5, preferably 1:1.7 to 1:3.1, more preferably 1:1.8 to 1:3, and in particular 1:1.9 to 1:2.9.

[0068] In one embodiment of the present invention, the solvent in step a) is not a non-polar solvent. It should be understood that a non-polar solvent has a dielectric constant (ε) less than 15. Non-polarity may alternatively or additionally be expressed by a dipole moment (μ) from 0 to 0.5.

[0069] In one embodiment of the present invention, the solvent in step a) is not selected from the group consisting of petroleum ether, ligroin, n-hexane, cyclohexane, heptane, di-n-butyl ether, xylene, toluene and benzene. In yet another embodiment of the present invention, the process does not comprise the addition of a solvent selected from the group consisting of petroleum ether, ligroin, n-hexane, cyclohexane, heptane, di-n-butyl ether, xylene, toluene and benzene.

[0070] In step b) the solution is cooled to a temperature in the range of 20 to 40°C, preferably 20 to 35°C, more preferably 20 to 30°C.

[0071] In one embodiment of the present invention, in step b) the solution is cooled to a temperature of 20°C to 40°C, preferably 22°C to 35°C, more preferably 25°C to 30°C, for a period of at least 10 minutes, preferably at least 15 minutes, more preferably at least 20 minutes, and in particular at least 25 minutes. In a preferred embodiment of the present invention, in step b) the solution is cooled to a temperature of 20°C to 30°C, preferably 22°C to 28°C, for Petition 870260057225, dated 12 / 06 / 2026, p. 28 / 56 / 34 a period of at least 10 minutes, preferably at least 15 minutes, more preferably at least 20 minutes, and in particular at least 25 minutes.

[0072] In one embodiment of the present invention, in step b) the solution is cooled to a temperature of 20°C to 40°C, preferably 22 to 35°C, more preferably 25 to 30°C, at a cooling rate of 10 to 100°C / hour, preferably 15 to 90°C / hour, more preferably 20 to 70°C / hour, and in particular 25 to 60°C / hour. In a preferred embodiment of the present invention, in step b) the solution is cooled to a temperature of 20°C to 30°C, preferably 22°C to 28°C, at a cooling rate of 10 to 100°C / hour, preferably 15 to 90°C / hour, more preferably 20 to 70°C / hour, and in particular 25 to 60°C / hour.

[0073] In one embodiment of the present invention, the cooling in step b) is carried out by means of a linear or non-linear cooling rate.

[0074] In one embodiment of the present invention, in step c) hexyl ester crystals of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid are added to the solution.

[0075] In one embodiment of the present invention, the solution containing seed crystals in step c) is stirred at a temperature of more than 20°C to less than 40°C, preferably 22 to 35°C and more preferably 25 to 30°C, for a period of 1 to 60 minutes, preferably 1 to 50 minutes, more preferably 2 to 40 minutes, and in particular 3 to 25 minutes.

[0076] In one embodiment of the present invention, in step d) the solution is cooled to a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below -5°C, and in particular below -7°C, for a period of at least 2 hours, preferably at least 3 hours, more preferably at least 4 hours, and in particular at least 5 hours. Petition 870260057225, dated 12 / 06 / 2026, p. 29 / 56 / 34

[0077] In one embodiment of the present invention, in step d) the solution is cooled to a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below -5°C, and in particular below -7°C, at a cooling rate of more than 4 to less than 20°C / hour, preferably from 4.5 to 15°C / hour, more preferably from 5 to 11°C / hour, and especially from 5 to 10°C / hour.

[0078] In one embodiment of the present invention, the cooling in step d) is carried out by means of a linear or non-linear cooling rate.

[0079] In one embodiment of the present invention, step d) further comprises stirring the resulting suspension at a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below -5°C, and in particular below -7°C, for at least 3 hours, preferably at least 4 hours, more preferably at least 5 hours, and in particular at least 6 hours.

[0080] In one embodiment of the present invention, step e) is carried out at a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below 5°C, and in particular below -7°C.

[0081] In one embodiment of the present invention, subsequent to step e), the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid isolated in crystalline form is suspended at least once more in a solvent at a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below -5°C, and in particular below -7°C. In one embodiment of the present invention, at least one additional suspension step is carried out at the same temperature as in step e). In this respect, the solvent used is a solvent with a boiling point of no more than 110°C, where the solvent is preferably the same solvent used previously in step a), plus Petition 870260057225, dated 12 / 06 / 2026, page 30 / 56 / 34 preferably, wherein the solvent is selected from methanol, ethanol, 1-propanol and isopropanol, and in particular is ethanol. After at least one additional suspension step, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in crystalline form is filtered at a temperature below 5°C, preferably below 0°C, more preferably below -3°C, even more preferably below 5°C, and in particular below -7°C.

[0082] In one embodiment of the present invention, the process further comprises the step of f) Wash the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a solvent, optionally an aqueous base, optionally a surfactant, and optionally water.

[0083] It should be understood that the washing step f) can be carried out with any known suitable solvent as described above in more detail. Preferably, the solvent in step f) is the solvent used in step a) of the process.

[0084] In one embodiment of the present invention, the aqueous base is present in the washing step f) and is a solution of potassium or sodium carbonate, a solution of potassium or sodium bicarbonate, a solution of potassium or sodium hydroxide, or an aqueous solution of ammonia. In a particular embodiment of the present invention, the aqueous base is present in step f) and is a solution of sodium carbonate.

[0085] In one embodiment of the present invention, step f) further comprises washing with an acidic solution. In this respect, inorganic acids such as aqueous hydrogen chloride solution and organic acids such as aqueous citric acid solution may be mentioned.

[0086] In one embodiment of the present invention, the surfactant is present in step f) and is selected from the group consisting of anionic surfactant, cationic surfactant, amphoteric surfactant and nonionic surfactant. Petition 870260057225, dated 12 / 06 / 2026, page 31 / 56 / 34

[0087] Surfactants used in cosmetic formulations that are derived from natural products and / or are biodegradable are preferred.

[0088] In one embodiment of the present invention, the surfactant is present in step f) and is selected from the group consisting of alkylbenzyl sulfonate, sodium lauryl sulfate, ammonium lauryl sulfate, disodium lauryl sulfosuccinate, cocoamphocarboxyglycinate, decyl polyglucoside, cetearyl alcohol, stearyl alcohol, cocamidopropyl betaine, decyl glucoside, glyceryl cocoate, sodium cocoyl isethionate, almond glycerides, sodium lauryl sulfoacetate, sodium lauroyl sarcosinate, sodium methyl cocoyl taurate, sucrose cocoate, polysorbate 20 and polysorbate 80, preferably sodium salt of dodecylbenzene sulfonic acid.

[0089] In one embodiment of the present invention, step f) is carried out at a temperature of at least -5°C, preferably at least -2°C, more preferably at least 0°C and, in particular, at least 3°C.

[0090] In one embodiment of the present invention, the process further comprises the step of g) Dry the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester. It should be understood that all appropriate drying methods may be applied.

[0091] In one embodiment of the present invention, the drying step g) is carried out under vacuum at a temperature below 55°C, preferably below 50°C. In another embodiment of the present invention, the drying step g) is carried out under vacuum at a temperature of 25 to 55°C, preferably 25 to 50°C, and in particular 30 to 45°C.

[0092] In one embodiment of the present invention, the process does not involve the addition of activated carbon.

[0093] In one embodiment of the present invention, the process does not comprise adsorption onto a bed of silicic acid. Petition 870260057225, dated 12 / 06 / 2026, p. 32 / 56 / 34

[0094] In a particular embodiment of the present invention, the process does not comprise adsorption onto a bed of activated carbon or silicic acid.

[0095] After drying, a free-flowing crystalline solid of hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is obtained.

[0096] In one embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a phthalic acid dialkyl ester content of less than 40 ppm, preferably less than 30 ppm, more preferably less than 15 ppm, even more preferably less than 10 ppm, and in particular less than 5 ppm. In a particularly preferred embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a phthalic acid dialkyl ester content of less than 4 ppm, preferably less than 3 ppm, more preferably less than 2 ppm, and in particular less than 1 ppm.

[0097] In this regard, it should be understood that the present invention provides a process for isolating crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a reduced phthalic acid dihexyl ester content (also known as dihexyl phthalate), preferably with a phthalic acid dihexyl ester content of less than 15 ppm, more preferably less than 10 ppm, even more preferably less than 5 ppm, even more preferably less than 2 ppm and, in particular, less than 1 ppm.

[0098] In one embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a colored impurity content of less than 5 ppm, preferably less than 3 ppm and, in particular, less than 1 ppm.

[0099] In this regard, the present invention provides a process for isolating the hexyl ester of crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid with a reduced Rhodamine B content, preferably with a Petition 870260057225, dated 12 / 06 / 2026, p. 33 / 56 / 34 Rhodamine B content less than 5 ppm, more preferably less than 3 ppm and, in particular, less than 1 ppm.

[00100] In one embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a Gardner value of 9 or less, preferably 8.8 or less, more preferably 8.6 or less, even more preferably 8.4 or less, and in particular 8.3 or less.

[00101] In one embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a solvent content of less than 500 ppm, preferably less than 400 ppm, more preferably less than 300 ppm, even more preferably less than 200 ppm, even more preferably less than 100 ppm, and in particular less than 50 ppm. In this respect, it should be understood that the solvent content referred to includes impurities derived from solvent residues of solvents with a boiling point above 110°C.

[00102] In one embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a 1-hexanol content of less than 400 ppm, preferably less than 200 ppm, more preferably less than 150 ppm, even more preferably less than 100 ppm, even more preferably less than 50 ppm, and in particular less than 40 ppm.

[00103] In a preferred embodiment of the present invention, the process provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a toluene content of less than 300 ppm, preferably less than 200 ppm, more preferably less than 150 ppm, even more preferably less than 100 ppm, even more preferably less than 40 ppm, and in particular less than 20 ppm.

[00104] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of Petition 870260057225, dated 12 / 06 / 2026, p. 34 / 56 / 34 at least 99%, preferably at least 99.2%, more preferably at least 99.4%, even more preferably at least 99.6%, and in particular more than 99.8%.

[00105] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a solvent content of less than 400 ppm, and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester alone has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 5 ppm, a solvent content of less than 400 ppm, a Gardner value of 8.3 or less, and a rhodamine B content of less than 1 ppm. Preferably, the solvents are selected from the group consisting of 1-hexanol, toluene, and mixtures thereof.

[00106] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a solvent content of less than 400 ppm, a Gardner value of less than 8.3, and a rhodamine B content of less than 1 ppm.

[00107] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 3 ppm, a toluene content of less than 300 ppm, a 1-hexanol content of less than 400 ppm, a rhodamine B content of less than 1 ppm and / or a Gardner value equal to or less than 8.3.

[00108] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 5 ppm, a solvent content of less than 100 ppm, and a Gardner value of less than 8.3. Preferably, the solvents are selected from the group consisting of Petition 870260057225, dated 12 / 06 / 2026, p. 35 / 56 / 34 1-hexanol, toluene, and mixtures thereof.

[00109] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm, and a Gardner value of 8.3 or less, and wherein preferably the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine B content of less than 1 ppm.

[00110] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 400 ppm, a toluene content of less than 300 ppm, and a Gardner value of 8.3 or less.

[00111] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a solvent content of less than 200 ppm, and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester alone has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 5 ppm, a solvent content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine B content of less than 1 ppm.

[00112] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a solvent content of less than 200 ppm, a Gardner value of less than 8.3, and a rhodamine B content of less than 1 ppm. Petition 870260057225, dated 12 / 06 / 2026, p. 36 / 56 / 34

[00113] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 3 ppm, a toluene content of less than 1 ppm, a 1-hexanol content of less than 200 ppm, a rhodamine B content of less than 1 ppm, and a Gardner value equal to or less than 8.3.

[00114] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a solvent content of less than 200 ppm, and a Gardner value of less than 8.3.

[00115] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 15 ppm, a solvent content of less than 200 ppm, and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester alone has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a solvent content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine B content of less than 1 ppm.

[00116] In one embodiment of the present invention, the isolated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 1 ppm, a solvent content of less than 200 ppm, a Gardner value of less than 8.3, and a rhodamine B content of less than 1 ppm.

[00117] In one embodiment, the present invention relates to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester crystals obtained according to the claimed process. Preferably, the crystals obtained have a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a solvent content of less than 200 ppm, and a Gardner value of 8.3 or less, more preferably a purity of at least 99%, a Petition 870260057225, dated 12 / 06 / 2026, p. 37 / 56 / 34 phthalic acid dihexyl ester content less than 5 ppm, solvent content less than 200 ppm, Gardner value equal to or less than 8.3 and rhodamine content less than 1 ppm. In another preferred embodiment, the crystals obtained have a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm and a Gardner value of 8.3 or less, more preferably a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 200 ppm, a Gardner value of 8.3 or less and a rhodamine content of less than 1 ppm.

[00118] The process according to the present invention provides 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a particularly low impurity content. Surprisingly, the process according to the present invention provides 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a particularly low phthalic acid dialkyl ester content. According to the present invention, the determination of phthalate esters and rhodamine-type impurities is preferably carried out by HPLC analysis. Preferably, the determination of solvent residues is carried out by GC analysis.

[00119] In one embodiment, the present invention relates to a crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a phthalic acid dialkyl ester content of less than 15 ppm, preferably less than 10 ppm, more preferably less than 5 ppm, even more preferably less than 2 ppm, and in particular less than 1 ppm.

[00120] In a particular embodiment, the present invention relates to a crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a phthalic acid dialkyl ester content of less than 15 ppm, preferably less than 10 ppm, more preferably less than 5 ppm, even more preferably less than 2 ppm, and in particular less than 1 ppm.

[00121] In one embodiment, the present invention relates to an ester Petition 870260057225, dated 12 / 06 / 2026, page 38 / 56 / 34 hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid having a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm, and a Gardner value of 8.3 or less, and preferably the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine content of less than 1 ppm.

[00122] In a preferred embodiment, the present invention relates to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a 1-hexanol content of less than 400 ppm, a toluene content of less than 300 ppm and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a 1-hexanol content of less than 200 ppm, a toluene content of less than 100 ppm and a Gardner value of 8.3 or less.

[00123] In one embodiment, the present invention relates to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a purity of at least 99%, a phthalic acid dialkyl ester content of less than 15 ppm, a solvent content of less than 200 ppm, and a Gardner value of 8.3 or less, and wherein preferably the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester has a purity of at least 99%, a phthalic acid dihexyl ester content of less than 5 ppm, a solvent content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine content of less than 1 ppm.

[00124] In one embodiment, the present invention relates to a body care product or a daily care composition comprising 2-(4'-diethylamino-2') hexyl ester crystals Petition 870260057225, dated 12 / 06 / 2026, page 39 / 56 / 34 hydroxybenzoyl)benzoic acid obtained according to the claimed process. In particular, the present invention relates to a sunscreen composition comprising 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester crystals obtained according to the claimed process.

[00125] In one embodiment, the present invention relates to the use of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester crystals obtained according to the claimed process as a UV filter in a body care product or in a daily care composition, in particular in a sun protection composition.

[00126] The present invention is further illustrated by the following examples. Examples Methods

[00127] The determination of hexyl ester of 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid and solvent residues was performed using GC analysis.

[00128] GC Agilent 6890 Plus with FID (flame ionization detector). Fused silica capillary column (100% dimethylpolysiloxane film (0.33 µm), e.g., Agilent 19091-60321, 12 m x 0.2 mm). Helium, constant flow, split 150:1, injector temperature 250°C, detector temperature 320°C, injection volume 1 pL. Gradient: 2 min T=80°C, 10°C / min (80-320°C), 4 min T=320°C.

[00129] External standards: Toluene, n-hexanol, 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, ethanol, 2-propanol.

[00130] The determination of phthalate esters and rhodamine-type impurities was performed using HPLC analysis.

[00131] Agilent 1290 HPLC with diode array detector (190 640 nm). Zorbax Eclipse XDB C8 HPLC column, 3x100mm, 1.8 pm (Agilent Nr. 993967-906). Petition 870260057225, dated 12 / 06 / 2026, page 40 / 56 / 34

[00132] Solvent A: Water / acetonitrile 9:1 + TBAHS (tetrabutylammonium hydrogen sulfate) 2 g / L. Solvent B: Acetonitrile (0.8 mL / min). Injection volume 5 pL, T=50°C. Gradient: t=0 min 100%A, 0%B / t=21 min, 0%A, 100%B / t=23 min, 0%A, 100%B / t=24 min, 100%A, 0%B (post-treatment time 4 min).

[00133] Rhodamine B: RT = 8.2 min (558 nm), Di-n-hexyl phthalate: RT (retention time) = 17.3 min (200 nm, sign subtraction of 356 nm). External standards: Rhodamine B, Di-n-hexyl phthalate.

[00134] The Gardner value was determined by measuring the spectral color of transparent molten 2-(4'-Diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (Lico 500 colorimeter, Hach Lange GmbH, Germany).

[00135] Analytical standards for calibration were performed using state-of-the-art standard methods. Example 1

[00136] Crude wet pink 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared according to US2005 / 0165099, example 2. The crude product is dried by suction.

[00137] Composition of the crude product: 93% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 7% solvent residues and impurities (81 ppm PSDHE, Gardner Value > 9).

[00138] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (299.8 g) is dissolved in ethanol (836.4 g) at 50°C, then cooled to 25°C within 30-50 min (linear cooling ramp). Then, pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals (0.012 g) are added and the mixture is stirred for 5-10 min at 25°C. After cooling to -10°C (10 h, linear cooling ramp), a crystal suspension is obtained and further stirred for 7 h at -10°C. The solids are separated by filtration at 10°C. The crystals are suspended in cold ethanol (167 g) and separated by filtration. Petition 870260057225, dated 12 / 06 / 2026, p. 41 / 56 / 34 under vacuum (-10°C). Subsequently, the temperature is increased to 5°C and the crystalline solid is successively washed with aqueous solution of Na2CO3 (668 g, 2% Na2CO3), aqueous solution of citric acid (670 g, 1% citric acid) and water. The product is dried under vacuum (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (258.1 g) as a nearly white free-flowing crystalline solid.

[00139] Pure product composition: 99.9% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 190 ppm 1-hexanol, 250 ppm toluene, 6 ppm PSDHE, Gardner value 8.1. Example 2

[00140] Crude wet pink 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared in accordance with US2005 / 0165099, example 2. The crude product is dried by suction.

[00141] Composition of the crude product: 92% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 8% solvent residues and impurities (81 ppm PSDHE, Gardner Value > 9).

[00142] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (302.7 g) is dissolved in ethanol (630.1 g) at 50°C, then cooled to 25°C within 30-50 min (linear cooling ramp). Then, pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals (0.012 g) are added and the mixture is stirred for 5-10 min at 25°C. After cooling to -10°C (10 h, linear cooling ramp), a crystal suspension is obtained and further stirred for 6 h at -10°C. The solids are separated by filtration at 10°C. The crystals are suspended in cold ethanol (130 to 190 g) and separated by vacuum filtration (-10°C, repeated four times). Subsequently, the temperature is increased to 5°C and the crystalline solid is successively washed with Na2CO3 / aqueous solution of sodium salt of dodecylbenzenesulfonic acid (504 g, 2% Na2CO3, 0.007 g sodium salt of Petition 870260057225, dated 12 / 06 / 2026, page 42 / 56 / 34 dodecylbenzenesulfonic acid), aqueous solution of citric acid (504 g, 1% citric acid) and water. The product is dried under vacuum (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (262.7 g) as a nearly white free-flowing crystalline solid.

[00143] Pure product composition: 99.9% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 310 ppm 1-hexanol, 38 ppm toluene, 2 ppm PSDHE, Gardner value 8.3. Example 3

[00144] Crude wet pink 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared in accordance with US2005 / 0165099, example 2. The crude product is vacuum dried at 120°C (rotary evaporator).

[00145] Composition of the crude product: 99.1% hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, 0.5% 1-hexanol, 0.2% toluene, 39.4 ppm Rhodamine B, 62 ppm PSDHE, Gardner Value 9.

[00146] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (448.7 g) is dissolved in ethanol (547.9 g) at 3750°C, then cooled from 37 to 25°C in 70 min (linear cooling ramp). Then, pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals (9.0 g) are added and the mixture is stirred for 220 min at 25°C. After cooling to -10°C (300 min, linear cooling ramp), a crystal suspension is obtained and further stirred for 6 to 8 hours at -10°C. The solids are separated by filtration at -10°C. The crystals are suspended in cold ethanol (130 to 330 g) and separated by vacuum filtration (-10°C, repeated three times). The product is dried under vacuum (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (425.1 g) as a nearly white, free-flowing crystalline solid.

[00147] Composition of the pure product: 99.9% hexyl ester of the acid Petition 870260057225, dated 12 / 06 / 2026, page 43 / 56 / 34 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, < 10 ppm 1-hexanol, 10 ppm toluene, 0.8 ppm PSDHE, 0.8 ppm Rhodamine B, Gardner value 7.0. Example 4

[00148] Crude wet pink 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared in accordance with US2005 / 0165099, example 2. The crude product is vacuum dried at 120°C (rotary evaporator).

[00149] Composition of the crude product: 99.1% hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, 0.5% 1-hexanol, 0.2% toluene, 39.4 ppm Rhodamine B, 62 ppm PSDHE, Gardner Value 9.

[00150] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (449.0 g) is dissolved in ethanol (548.0 g) at 3750°C, then cooled from 37 to 25°C in 70 min (linear cooling ramp). Then, pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals (9.1 g) are added and the mixture is stirred for 220 min at 25°C. After cooling to -10°C (300 min, linear cooling ramp), a crystal suspension is obtained and further stirred for 6 to 8 hours at -10°C. The solids are separated by filtration at -10°C. The crystals are suspended in cold ethanol (130 to 452 g) and separated by vacuum filtration (-10°C, repeated three times). The product is dried under vacuum (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (426.0 g) as a nearly white, free-flowing crystalline solid.

[00151] Composition of the pure product: 99.7% hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, < 10 ppm 1-hexanol, 10 ppm toluene, 0.8 ppm PSDHE, 0.8 ppm Rhodamine B, Gardner value 7.0. Example 5

[00152] The crude wet pink 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared from Petition 870260057225, dated 12 / 06 / 2026, page 44 / 56 / 34 in accordance with US2005 / 0165099, example 2. The crude product is vacuum dried at 120°C (rotary evaporator).

[00153] Composition of crude product: 98.5% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 1.0% 1-hexanol, 0.1% toluene, 34.0 ppm Rhodamine B, 80 ppm PSDHE, Gardner value 8.7.

[00154] The crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (449.0 g) is dissolved in ethanol (550.1 g) at 3750°C, then cooled from 37 to 25°C in 70 min (linear cooling ramp). Next, pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester seed crystals (9.0 g) are added and the mixture is stirred for 220 min at 25°C. After cooling to -10°C (300 min, linear cooling ramp), a crystal suspension is obtained and further stirred for 6 to 8 hours at -10°C. The solids are separated by filtration at -10°C. The crystals are suspended in cold ethanol (130 to 450 g) and separated by vacuum filtration (-10°C, repeated three times).Subsequently, the temperature is increased to 5 to 10°C and the crystalline solid is washed with water (750 g). The product is dried under vacuum (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (428.1 g) as a nearly white free-flowing crystalline solid.

[00155] Composition of the pure product: 99.8% hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, 30 ppm 1-hexanol, 7 ppm toluene, 0.9 ppm PSDHE, 0.6 ppm Rhodamine B, Gardner value 7.1. Example 6

[00156] Crude wet pink 2-(4'-diethylamino-2'hydroxybenzoyl)benzoic acid hexyl ester with hexanol is prepared in accordance with US2005 / 0165099, example 2. The crude product is vacuum dried at 120°C (rotary evaporator).

[00157] Composition of the crude product: 98.5% hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, 1.0% 1-hexanol, 0.1% of Petition 870260057225, dated 12 / 06 / 2026, p. 45 / 56 / 34 toluene, 34.0 ppm Rhodamine B, 80 ppm PSDHE, Gardner value 8.7.

[00158] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (449.0 g) is dissolved in 2-propanol (550 g) at 37 to 50°C, then cooled from 37 to 25°C in 70 min (linear cooling ramp). Then, seed crystals of pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (9.1 g) are added and the mixture is stirred for 220 min at 25°C. After cooling to 0°C (300 min, linear cooling ramp), a crystal suspension is obtained and further stirred for 6 to 8 hours at 0°C. The solids are separated by filtration at 0°C. The crystals are suspended in cold 2-propanol (307 to 338 g) and separated by vacuum filtration (-0°C, repeated three times). Subsequently, the temperature is increased to 5 to 15°C and the crystalline solid is washed with water (615 g).The product is vacuum dried (45°C) to give pure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (432.4 g) as a nearly white free-flowing crystalline solid.

[00159] Pure product composition: 99.8% 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 65 ppm 1-hexanol, 15 ppm toluene, 1.7 ppm PSDHE, 2.2 ppm rhodamine B, Gardner value 7.1. Petition 870260057225, dated 12 / 06 / 2026, pages 46 / 56

Claims

1 / 3 CLAIMS 1. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, characterized by having a phthalic acid dialkyl ester content of less than 15 ppm.

2. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to claim 1, characterized in that it has a phthalic acid dialkyl ester content of less than 10 ppm, preferably less than 5 ppm, more preferably less than 2 ppm and, even more preferably, less than 1 ppm.

3. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to claim 1, characterized in that it has a dihexyl ester content of phthalic acid of less than 1 ppm.

4. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 3, characterized in that it has a purity of at least 99%.

5. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 4, characterized in that it has a purity of at least 99.2%, preferably at least 99.4%.

6. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 5, characterized in that it has a purity of at least 99.6%, preferably greater than 99.8%.

7. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 6, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is crystalline and has a solvent content of less than 500 ppm, preferably less than 400 ppm, more preferably less than 300 ppm, even more preferably less than 200 ppm, even more preferably less than 100 ppm and, in particular, less than 50 ppm.

8. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 7, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is crystalline and has a 1-hexanol content of less than 400 ppm, preferably less than 200 ppm, more preferably less than 150 ppm, even more preferably less than 100 ppm, even more preferably less than 50 ppm and, in particular, less than 40 ppm.

9. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 8, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is crystalline and has a toluene content of less than 300 ppm, preferably less than 200 ppm, more preferably less than 150 ppm, even more preferably less than 100 ppm, even more preferably less than 40 ppm and, in particular, less than 20 ppm.

10. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 9, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is crystalline and has a Gardner value of 9 or less, preferably 8.8 or less, more preferably 8.6 or less, even more preferably 8.4 or less, and in particular 8.3 or less.

11. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 10, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid is crystalline and has a colored impurity content of less than 5 ppm, preferably less than 3 ppm and, in particular, less than 1 ppm.

12. 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, according to any one of claims 1 to 11, characterized in that the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is crystalline and has a rhodamine B content of less than 5 ppm, more preferably less than 3 ppm and, in particular, less than 1 ppm.

13. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 12, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 5 ppm, a solvent content of less than 100 ppm, and a Gardner value of 8.3 or less.

14. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to any one of claims 1 to 13, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a solvent content of less than 200 ppm, and a Gardner value of 8.3 or less.

15. Hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid, according to claim 13, characterized in that the hexyl ester of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid has a purity of at least 99%, a phthalic acid dialkyl ester content of less than 1 ppm, a solvent content of less than 200 ppm, a Gardner value of 8.3 or less, and a rhodamine B content of less than 1 ppm. Petition 870260057225, dated 12 / 06 / 2026, pp. 49 / 56