Process for preparing ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate

Abstract

A novel method for the synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate is described herein.

Description

Technical Field

[0001] Cross - reference to related applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 933,553, filed on November 11, 2019.

[0002] The present disclosure is directed to a novel method for synthesizing ethyl 3 - bromo - 1-(3 - chloropyridin - 2 - yl)-1H - pyrazole - 5 - carboxylate. Compounds prepared by the methods disclosed herein are useful in the preparation of certain anthranilamide compounds that are of interest as insecticides, such as the insecticides chlorantraniliprole and cyantraniliprole.

Background Art

[0003] Ethyl 3 - bromo - 1-(3 - chloropyridin - 2 - yl)-1H - pyrazole - 5 - carboxylate is an intermediate in the production of 3 - bromo - N - [4 - chloro - 2 - methyl - 6 - [(methylamino)carbonyl]phenyl]-1-(3 - chloro - 2 - pyridinyl)-1H - pyrazole - 5 - carboxamide and 3 - bromo - 1-(3 - chloropyridin - 2 - yl)-N - [4 - cyano - 2 - methyl - 6 - [N - methylcarbamoyl]phenyl]-1H - pyrazole - 5 - carboxamide.

[0004] As disclosed in Patent International Publication No. 03016283A1 pamphlet, ethyl 3 - bromo - 1-(3 - chloropyridin - 2 - yl)-1H - pyrazole - 5 - carboxylate is produced from ethyl 3 - bromo - 1-(3 - chloropyridin - 2 - yl)-4,5 - dihydro - 1H - pyrazole - 5 - carboxylate by an oxidation reaction in an acetonitrile system in the presence of potassium persulfate using sulfuric acid as a catalyst. The reported yield is about 75 - 80%.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] The present disclosure provides a novel method useful for the preparation of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate and its derivatives. There are numerous advantages of the method of the present disclosure compared with the conventional methods, and the advantages include improved overall yield, cost reduction, and reduction of process hazards.

[0007] An overall yield of about 88% is obtained by the disclosed method.

MEANS FOR SOLVING THE PROBLEMS

[0008] In one aspect, a method for preparing a compound of formula II

CHEMICAL FORMULA

CHEMICAL FORMULA

DETAILED DESCRIPTION OF THE INVENTION

[0009] As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", "characterized by", and any other variations thereof are intended to address non-exclusive inclusion subject to any limitations explicitly stated. For example, a composition, mixture, process, or method comprising a series of elements is not necessarily limited to only those elements, and may include other elements not explicitly listed and not specific to such composition, mixture, process, or method.

[0010] The transitional phrase "consisting of" excludes any element, step, or component not specified. In the case of a claim, this will exclude the incorporation of materials other than those described, except for impurities normally associated therewith, from that claim. When the phrase "consisting of" appears in a clause of the body of a claim rather than immediately following the preamble, this limits only the elements recited in that clause, and other elements are not excluded from the claim as a whole.

[0011] The transitional phrase "consisting essentially of" is used to define a composition or method that includes those materials, steps, features, components, or elements literally disclosed, plus additional materials, steps, features, components, or elements that do not substantially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" occupies an intermediate area between "comprising" and "consisting of".

[0012] If the invention or a part thereof is defined using terms without limitations such as "comprising" (unless otherwise specified), it will be readily understood that such description should be construed as also being described using the terms "consisting essentially of" or "consisting of".

[0013] Furthermore, unless clearly indicated to the contrary, "or" means an inclusive or and not an exclusive or. For example, the condition "A or B" is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); and both A and B are true (or exist).

[0014] Also, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be non - limiting with respect to the number of instances (i.e., occurrences) of that element or component. Thus, "a" or "an" should be read as including one or at least one, and an element or component in the singular form of a word form includes the plural as well, unless the number is clearly singular.

[0015] In this specification, the term "about" means ±10% of that value.

[0016] The term "eq" means the amount of a substance that reacts with (or is equivalent to) any amount of another substance in a given chemical reaction.

[0017] The term "% assay" means dividing the content of the desired compound by the total weight of the sample.

[0018] In the case of alone or in any of the words or expressions of a compound such as "haloalkyl" or "halogenated alkyl", the term "halogen" includes fluorine, chlorine, bromine, or iodine. Further, when used in a word or expression of a compound such as "haloalkyl" or "halogenated alkyl", the alkyl may be partially or completely substituted with halogen atoms, which may be the same or different in each case.

[0019] For example, when a group such as R 4 contains a substituent that may be hydrogen and this substituent is interpreted as hydrogen, this is recognized as equivalent to the group being unsubstituted.

[0020] The specific compounds of the present invention can exist as one or more stereoisomers. Examples of various stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. Those skilled in the art will recognize that a stereoisomer may be more active and / or exhibit beneficial effects when it is more concentrated than another stereoisomer or when it is separated from another stereoisomer. Further, those skilled in the art understand the methods for separating, concentrating, and / or selectively preparing the above stereoisomers.

[0021] Embodiments of the present disclosure include the following.

[0022] Embodiment 1. A method for preparing a compound of formula II [Chemical formula] (wherein R8 is selected from hydrogen and C1-C4 alkyl; each of R2-R7 is independently selected from hydrogen, halogen, C1-C4 alkyl, and halogenated C1-C4 alkyl) comprising: I) A) A first amount of a compound of formula I [Chemical formula] (Here, R1 is selected from hydrogen and C1-C4 alkyl; each of R2-R7 is independently selected from hydrogen, halogen, C1-C4 alkyl, and halogenated C1-C4 alkyl) and; B) an oxidizing agent; C) an organic solvent to form a mixture comprising; II) heating the above mixture; III) adding an acid to the above mixture; IV) adding a second amount of the compound of formula I to the above mixture; V) completing the reaction of the above mixture, and a method comprising.

[0023] Embodiment 2. The method of Embodiment 1, wherein the oxidizing agent is selected from hydrogen peroxide, organic peracids, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate, sodium monopersulfate, potassium permanganate, and combinations thereof.

[0024] Embodiment 3. The method of Embodiment 1, wherein the oxidizing agent is potassium persulfate.

[0025] Embodiment 4. The method of Embodiment 1, wherein the oxidizing agent is present in the mixture in an amount in the range of about 1.0 eq to about 2.0 eq.

[0026] Embodiment 5. The method of Embodiment 1, wherein the oxidizing agent is present in the mixture in an amount in the range of about 1.3 eq to about 1.7 eq.

[0027] Embodiment 6. The method of Embodiment 1, wherein the oxidizing agent has a D50 particle size in the range of about 10 μm to about 200 μm.

[0028] Embodiment 7. The method of Embodiment 1, wherein the oxidizing agent has a D50 particle size in the range of about 20 μm to about 100 μm.

[0029] Embodiment 8. The method of Embodiment 1, wherein the oxidizing agent has a D50 particle size in the range of about 30 μm to about 80 μm.

[0030] Embodiment 9. The method of Embodiment 1, wherein the oxidizing agent has a D50 particle size in the range of about 40 μm to about 60 μm.

[0031] Embodiment 10. The method of Embodiment 1, wherein the solvent is selected from ethers, esters, aprotic organic solvents, and combinations thereof.

[0032] Embodiment 11. The method of Embodiment 10, wherein the ether is selected from tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, and combinations thereof.

[0033] Embodiment 12. The method of Embodiment 10, wherein the ester is selected from ethyl acetate, isopropyl acetate, dimethyl carbonate, butyl acetate, and combinations thereof.

[0034] Embodiment 13. The method of Embodiment 10, wherein the aprotic organic solvent is selected from N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolidinone, acetonitrile, and combinations thereof.

[0035] Embodiment 14. The method of Embodiment 10, wherein the aprotic organic solvent is acetonitrile.

[0036] Embodiment 15. The method of Embodiment 1, wherein the first amount of the compound of Formula I is about 5 wt% to about 40 wt% of the total amount of the compound of Formula I.

[0037] Embodiment 16. The method of Embodiment 1, wherein the first amount of the compound of Formula I is present in the mixture at a concentration in the range of about 10 wt% to about 30 wt% of the total amount of the compound of Formula I.

[0038] Embodiment 17. The method of Embodiment 1, wherein the acid is selected from inorganic acids, organic acids, and combinations thereof.

[0039] Embodiment 18. The method of Embodiment 17, wherein the organic acid is selected from acetic acid, propanoic acid, p-toluenesulfonic acid, benzoic acid, and combinations thereof.

[0040] Embodiment 19. The method of Embodiment 17, wherein the inorganic acid is selected from sulfuric acid, phosphoric acid, oleum, hydrobromic acid, hydrochloric acid, and combinations thereof.

[0041] Embodiment 20. The method of Embodiment 17, wherein the inorganic acid is sulfuric acid.

[0042] Embodiment 21. The method of Embodiment 1, wherein the acid is present in the mixture in an amount in the range of about 0.05 eq to about 1.5 eq.

[0043] Embodiment 22. The method of Embodiment 1, wherein the acid is present in the mixture in an amount less than about 0.2 eq.

[0044] Embodiment 23. The method of Embodiment 1, wherein the method step of forming the mixture is carried out at a temperature in the range of about 0 °C to about 60 °C.

[0045] Embodiment 24. The method of Embodiment 1, wherein the method step of forming the mixture is carried out at a temperature in the range of about 15 °C to about 35 °C.

[0046] Embodiment 25. The method of Embodiment 1, wherein the method step of forming the mixture is carried out at room temperature.

[0047] Embodiment 26. The method of Embodiment 1, wherein the temperature of the mixture is raised to a temperature in the range of about 50 °C to about 82 °C by the method step of heating the mixture.

[0048] Embodiment 27. The method of Embodiment 1, wherein the temperature of the mixture is raised to a temperature in the range of about 55 °C to about 65 °C by the method step of heating the mixture.

[0049] Embodiment 28. The method of Embodiment 1, wherein the method step of adding a second amount of the compound of Formula I to the mixture is carried out at a temperature in the range of about 50 °C to about 82 °C.

[0050] Embodiment 29. The method step of adding a second amount of the compound of formula I to the mixture is carried out at a temperature in the range of about 65 °C to about 82 °C, the method of Embodiment 1.

[0051] Embodiment 30. The method step of adding a second amount of the compound of formula I includes adding the second amount of the compound of formula I discontinuously, the method of Embodiment 1.

[0052] Embodiment 31. The method step of adding a second amount of the compound of formula I includes adding the second amount of the compound of formula I continuously, the method of Embodiment 1.

[0053] Embodiment 32. The method step of adding a second amount of the compound of formula I includes adding the second amount of the compound of formula I dropwise, the method of Embodiment 1.

[0054] Embodiment 33. The method step of adding a second amount of the compound of formula I is carried out over a time in the range of about 3 hours to about 7 hours, the method of Embodiment 1.

[0055] Embodiment 34. The method step of adding a second amount of the compound of formula I is carried out over a time in the range of about 3.5 hours to about 4.5 hours, the method of Embodiment 1.

[0056] Embodiment 35. The second amount of the compound of formula I is more than the first amount of the compound of formula I, the method of Embodiment 1.

[0057] Embodiment 36. The second amount of the compound of formula I is at least twice the first amount of the compound of formula I, the method of Embodiment 1.

[0058] Embodiment 37. The second amount of the compound of formula I is about 70% by weight of the total amount of the compound of formula I, the method of Embodiment 1.

[0059] Embodiment 38. The first amount of the compound of formula I is about 30% by weight of the total amount of the compound of formula I, the method of Embodiment 1.

[0060] Embodiment 39. The method of Embodiment 1, wherein at least one method step further comprises detecting the O2 content of the mixture using an oxygen sensor.

[0061] Embodiment 40. The method of Embodiment 1, wherein the method step of heating the mixture is carried out in the absence of O2.

[0062] Embodiment 41. The method of Embodiment 1, wherein less than about 0.5 wt% of O2 is produced.

[0063] Embodiment 42. The method of Embodiment 1, wherein no O2 is produced.

[0064] Embodiment 43. The method of Embodiment 1, wherein at least one method step further comprises stirring the mixture.

[0065] In one aspect, ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate is prepared by the method shown in Scheme 1.

Chemical formula

[0066] In one aspect, a compound of formula II is prepared by the method shown in Scheme 2. The R group is defined anywhere in the present disclosure.

Chemical formula

[0067] This aspect includes forming a mixture comprising a first amount of a compound of formula I, an oxidizing agent, and an organic solvent, heating the mixture, adding an acid to the mixture, adding a second amount of a compound of formula I to the mixture, and completing the reaction of the mixture.

[0068] In one embodiment, the oxidizing agent is selected from hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate, sodium monopersulfate, potassium permanganate, and combinations thereof. In another embodiment, the oxidizing agent is potassium persulfate. In one embodiment, the oxidizing agent is present in the mixture in an amount in the range of about 1.0 eq to about 2.0 eq. In another embodiment, the oxidizing agent is present in the mixture in an amount in the range of about 1.3 eq to about 1.7 eq. In one embodiment, the oxidizing agent has a D50 particle size in the range of about 10 μm to about 200 μm. In another embodiment, the oxidizing agent has a D50 particle size in the range of about 20 μm to about 100 μm. In another embodiment, the oxidizing agent has a D50 particle size in the range of about 30 μm to about 80 μm. In another embodiment, the oxidizing agent has a D50 particle size in the range of about 40 μm to about 60 μm.

[0069] In one embodiment, the solvent is selected from ethers, esters, aprotic organic solvents, and combinations thereof. In another embodiment, the solvent is an ether selected from tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, and combinations thereof. In another embodiment, the solvent is an ester selected from ethyl acetate, isopropyl acetate, dimethyl carbonate, butyl acetate, and combinations thereof. In one embodiment, the solvent is an aprotic organic solvent selected from N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolidinone, acetonitrile, and combinations thereof. In another embodiment, the solvent is acetonitrile.

[0070] In one embodiment, the first amount of the compound of Formula I is about 5 wt% to about 40 wt% of the total amount of the compound of Formula I. In another embodiment, the first amount of the compound of Formula I is about 10 wt% to about 30 wt% of the total amount of the compound of Formula I.

[0071] In one embodiment, the acid is selected from inorganic acids, organic acids, and combinations thereof. In another embodiment, the acid is an organic acid selected from acetic acid, propanoic acid, p-toluenesulfonic acid, benzoic acid, and combinations thereof. In another embodiment, the acid is an inorganic acid selected from sulfuric acid, phosphoric acid, oleum, hydrobromic acid, hydrochloric acid, and combinations thereof. In another embodiment, the acid is sulfuric acid. In one embodiment, the acid is present in the mixture in an amount within the range of about 0.05 eq to about 1.5 eq. In another embodiment, the acid is present in the mixture in an amount less than about 0.2 eq.

[0072] In one embodiment, the method step of forming the mixture is carried out at a temperature within the range of about 0 °C to about 60 °C. In another embodiment, the method step of forming the mixture is carried out at a temperature within the range of about 15 °C to about 35 °C. In another embodiment, the method step of forming the mixture is carried out at room temperature. In one embodiment, the method step of forming the mixture includes stirring the mixture.

[0073] In one embodiment, the method step of heating the mixture raises the temperature of the mixture to a temperature within the range of about 50 °C to about 82 °C. In another embodiment, the method step of heating the mixture raises the temperature of the mixture to a temperature within the range of about 55 °C to about 65 °C. In one embodiment, the method step of heating the mixture includes stirring the mixture.

[0074] In one embodiment, the method step of adding the second amount of the compound of Formula I to the mixture is carried out at a temperature in the range of about 50 °C to about 82 °C. In another embodiment, the method step of adding the second amount of the compound of Formula I to the mixture is carried out at a temperature in the range of about 50 °C to about 82 °C. In one embodiment, the method step of adding the second amount of the compound of Formula I includes adding the second amount of the compound of Formula I discontinuously. In one embodiment, the method step of adding the second amount of the compound of Formula I includes adding the second amount of the compound of Formula I continuously. In another embodiment, the method step of adding the second amount of the compound of Formula I includes adding the second amount of the compound of Formula I dropwise. In one embodiment, the method step of adding the second amount of the compound of Formula I is carried out over a time in the range of about 3 hours to about 7 hours. In another embodiment, the method step of adding the second amount of the compound of Formula I is carried out over a time in the range of about 3.5 hours to about 4.5 hours. In one embodiment, the method step of adding the second amount of the compound of Formula I includes stirring the mixture.

[0075] In one embodiment, the second amount of the compound of Formula I is more than the first amount of the compound of Formula I. In another embodiment, the second amount of the compound of Formula I is at least twice the first amount of the compound of Formula I. In one embodiment, the second amount of the compound of Formula I is about 70% by weight of the total amount of the compound of Formula I. In another embodiment, the first amount of the compound of Formula I is about 30% by weight of the total amount of the compound of Formula I. In one embodiment, the second amount of the compound of Formula I is about 80% by weight of the total amount of the compound of Formula I. In another embodiment, the first amount of the compound of Formula I is about 20% by weight of the total amount of the compound of Formula I. In one embodiment, the second amount of the compound of Formula I is about 90% by weight of the total amount of the compound of Formula I. In another embodiment, the first amount of the compound of Formula I is about 10% by weight of the total amount of the compound of Formula I. In one embodiment, the second amount of the compound of Formula I is about 95% by weight of the total amount of the compound of Formula I. In another embodiment, the first amount of the compound of Formula I is about 5% by weight of the total amount of the compound of Formula I.

[0076] In one embodiment, at least one method step further includes detecting the O2 content of the mixture using an oxygen sensor. In one embodiment, the method step of heating the mixture is performed in the absence of O2. In one embodiment, this method produces less than about 0.5 wt% O2. In another embodiment, this method does not produce O2. The low and / or undetectable production of O2 improves the safety of the process.

Examples

[0077] Without further elaboration, it is believed that one of ordinary skill in the art can, using the above description, utilize the present invention to its fullest extent. Accordingly, the following examples are to be construed as merely illustrative and not in any way limiting of the present disclosure. The starting materials for the following examples are not necessarily prepared by the specific preparative procedures described in the procedures of other examples. It should also be understood that any numerical range recited herein includes every value from the lower limit to the upper limit. For example, if a range is described as 10 - 50, values such as 12 - 30, 20 - 40, or 30 - 50 are intended to be explicitly recited herein. These are merely exemplary values, and any numerical values between the recited minimum and maximum values, as well as any possible combinations of the values at both ends, should be considered to be explicitly disclosed in this application.

[0078] Comparative Example 1. Method for Monitoring Oxygen Generation Add 153 g of potassium persulfate, 450 g of acetonitrile, and other starting materials to a 2 L flask equipped with a cooler, thermometer, dropping funnel, and nitrogen inlet tube. Attach an oxygen sensor on top of the cooler. Replace the air in the reactor by flowing nitrogen at a rate of 0.55 L / min. After the oxygen sensor shows an oxygen level of 0.0%, heat the mixture to 60°C. Next, add 4.0 g of sulfuric acid to the mixture and maintain the heating and reflux of the mixture. Monitor and record the oxygen level throughout this process.

[0079] Comparative Example 2. Single addition of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate at the start of the reaction 174 g of potassium persulfate (1.6 eq), 780 g of 17% ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate in acetonitrile, and 40 g of concentrated sulfuric acid (1.0 eq) are added to the reactor. The reaction mixture is stirred and heated to 65 °C. The reaction shows a distinct exotherm and thus refluxes by self-heating. The reaction mixture is maintained at reflux for an additional 3 - 4 hours to complete the reaction. Throughout the process, no oxygen is detected. At 70 °C, 350 g of water is added to the mixture, and phase separation is carried out using potassium bisulfate to remove the waste water. The solvent is removed and then crystallized, and approximately 107 g of dry product of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate is obtained at approximately 96% assay and approximately 78% yield.

[0080] Example 1. Addition of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate at the start and after the start of the reaction 100 g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (40% in acetonitrile), 153 g of potassium persulfate (1.4 eq), and 450 g of acetonitrile are added to a reactor. The reaction mixture is stirred, heated to 60 °C, and then 4.0 g of concentrated sulfuric acid (0.1 eq) is added to the mixture. The reaction mixture is maintained at reflux for 1 hour, and then 230 g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (40% in acetonitrile) is added dropwise over 3 to 5 hours. After all the materials are added, the reaction mixture is maintained at reflux for an additional 1 to 2 hours to complete the reaction. Throughout the process, no oxygen is detected. 350 g of water is added to the mixture at 70 °C, and phase separation is carried out using potassium bisulfate to remove the waste water. After removing the solvent and then crystallizing, a dry product of approximately 120 g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate is obtained with a purity of approximately 97% and a yield of approximately 88%.

[0081] The descriptions provided herein use examples to illustrate the present disclosure, including the best mode, and to enable those skilled in the art to practice the present disclosure, such as the manufacture and use of any device or system and the implementation of any method included. The patentable scope of the present disclosure is defined by the scope of the claims and may include other examples that those skilled in the art can envision. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims or if they include equivalent structural elements with only minor differences from the literal language of the claims.

Claims

1. A method for preparing a compound of formula II, 【Chemical 1】 (Here, R 8 is selected from hydrogen and C 1 to C 4 alkyl; R 2 ~R 7 Each of which is independently hydrogen, halogen, C 1 ~C 4 alkyl, and halogenated C 1 ~C 4 (selected from alkyl)) comprising: I) A) A first amount of a compound of formula I 【Chemical 2】 (Here, R 1 is selected from hydrogen and C 1 to C 4 alkyl; R 2 ~R 7 Each of which is independently hydrogen, halogen, C 1 ~C 4 alkyl, and halogenated C 1 ~C 4 (selected from alkyl)); B) An oxidizing agent; C) An organic solvent, to form a mixture comprising; II) heating the mixture; III) adding an acid to the mixture; IV) adding a second amount of the compound of formula I to the mixture; V) completing the reaction of the mixture, a method comprising.

2. The method according to claim 1, wherein the oxidizing agent is selected from hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate, sodium monopersulfate, potassium permanganate, and combinations thereof.

3. The method according to claim 1, wherein the oxidizing agent is present in the mixture in an amount in the range of 1.0 eq to 2.0 eq.

4. The method according to claim 1, wherein the oxidizing agent has a D50 particle size in the range of 10 μm to 200 μm.

5. The method according to claim 1, wherein the solvent is selected from ethers, esters, aprotic organic solvents, and combinations thereof.

6. The method according to claim 1, wherein the first amount of the compound of formula I is 5% to 40% by weight of the total amount of the compound of formula I.

7. The method according to claim 1, wherein the acid is selected from inorganic acids, organic acids, and combinations thereof.

8. The method according to claim 1, wherein the acid is present in the mixture in an amount in the range of 0.05 eq to 1.5 eq.

9. The method according to claim 1, wherein the acid is present in the mixture in an amount less than 0.2 eq.

10. The method according to claim 1, wherein the method step of forming the mixture is carried out at a temperature in the range of 0 °C to 60 °C.

11. The method according to claim 1, wherein the temperature of the mixture is raised to a temperature in the range of 50 °C to 82 °C by the method step of heating the mixture.

12. The method according to claim 1, wherein the method step of adding the second amount of the compound of formula I comprises adding the second amount of the compound of formula I discontinuously.

13. The method according to claim 1, wherein the method step of adding the second amount of the compound of formula I comprises adding the second amount of the compound of formula I continuously.

14. The method according to claim 1, wherein the method step of adding the second amount of the compound of formula I comprises adding the second amount of the compound of formula I dropwise.

15. The method according to claim 1, wherein the step of adding the second amount of the compound of formula I is carried out over a time in the range of 3 to 7 hours.

16. The method according to claim 1, wherein the second amount of the compound of formula I is more than the first amount of the compound of formula I.

17. The method according to claim 1, wherein the second amount of the compound of formula I is at least twice the first amount of the compound of formula I.

18. The method according to claim 1, wherein the second amount of the compound of formula I is at least 70% by weight of the total amount of the compound of formula I.

19. The method according to claim 1, wherein the first amount of the compound of formula I is less than 30% by weight of the total amount of the compound of formula I.

20. The method according to claim 1, wherein at least one method step further comprises stirring the mixture.

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