KR101142283B1 - Novel Process For Preparation Of 2-Aminothiazole Carboxamide Derivatives - Google Patents

Abstract

The present invention provides a process for preparing a 2-aminothiazole carboxamide derivative of the formula (1) using a thiocarbamyl compound in the presence of a base. Such a preparation method can produce a compound of the formula (1) with a high reaction yield in a short period of time under mild conditions. By selecting a preferable solvent to be provided in the production method of the present invention, side reactions can be suppressed, It is possible to substantially prevent the decomposition of the catalyst.

(1)

(One)

( R < ¹ > and R < ² > are as defined in the specification)

Description

[0001] The present invention relates to novel 2-aminothiazole carboxamide derivatives,

The present invention relates to a novel process for the preparation of 2-aminothiazole carboxamide derivatives of formula (I), and more particularly to the use of a specific thiocarbamyl compound (II) The method comprising:

(1)

(One)

Wherein R ¹ is C _1-5 straight chain or branched alkyl, C _1-5 haloalkyl or C _3-6 cycloalkyl and R ² is C _1-3 alkyl or C _1-3 haloalkyl.

The compound of formula (1) is a sterilizing substance used in the eradication of plant diseases caused by bacteria of the genus Mycobacterium tuberculosis and bacteria of the genus Mycobacterium. Korean Patent Laid-Open Publication No. 94-19960 (entitled New 2-aminothiazole carboxamide derivatives, Methods for their preparation and their use for combating plant pathogens). Also, Korean Patent Laid-Open Publication No. 97-24120 discloses a process for producing 2-aminothiazole carboxamide derivatives containing the compound of formula (1). This method involves the use of 2-aminothiazolecarboxylic acid as an intermediate. From the industrial viewpoint, there is a problem that the number of process steps is large in obtaining an intermediate, and the productivity is low, which is uneconomical.

As a method for improving the above problems, the present applicant has proposed a process for preparing the compound of Formula 1 by reacting a thiophene acetamide compound of the following formula (3) with an iminothiourea compound of the following formula (4) -40539 and international patent application WO 00/18766.

(4)

(4)

(3)

(3)

In this formula,

R ¹ and R ² are the same as in the formula (1);

R < ⁷ > is phenyl, each of which is independently substituted with 1 to 5 of chlorine, methoxy, ethoxy, phenoxy or nitro groups;

Y is a leaving group such as chloride, bromide and the like.

This can be represented by the following reaction formula (1).

Scheme 1

Compared with the first method using 2-aminothiazolecarboxylic acid as an intermediate (Korean Patent Laid-Open No. 97-24120), the method of Reaction Scheme 1 is more economical in terms of industrial processes to be.

However, the reaction scheme (1) does not have a high reaction yield (about 70-75%), and therefore, a more economical production process capable of improving it is required. In addition, since only an alcohol compound is used as a solvent, subcomponents can be generated by side reactions of such alcohols, and decomposition of reactants and products due to the use of an excess amount of base (1.5 equivalents) can be improved.

Therefore, the inventors of the present invention have discovered a completely new manufacturing method after intensive research and various experiments, and confirmed that the manufacturing method solves the problems of the prior art as described above and the technical problems requested from the past . That is, the objective compound according to the present invention can produce a target compound at a high reaction yield in a short time under mild reaction conditions, and in the selection of a more preferable solvent, the side reaction can be suppressed by using no alcohol, The decomposition of the reactants can be substantially prevented.

Specifically, the process for preparing a compound of formula (I) according to the present invention comprises reacting a thiocarbamyl compound of formula (II) with a thiophene acetamide compound of formula (III) in the presence of a base:

(1)

(One)

(2)

(2)

(3)

(3)

In this formula,

R ¹ is C _1-5 straight chain or branched alkyl, C _1-5 haloalkyl or C _3-6 cycloalkyl;

R ² is C _1-3 alkyl or C _1-3 haloalkyl;

R ³ is NH ₂ , NR ⁴ R ⁵ or OR ⁶ ,

In this formula,

R ⁴ and R ⁵ are independently C _1-3 alkyl, or substituted phenyl, (phenyl) unsubstituted one another, - (CH ₂₎ n- or _{- (CH 2) 2 -X- (} CH 2) 2 - , and Wherein n is 4 or 5 and X is O, NH or S;

R ⁶ is C _1-3 alkyl;

Y is a leaving group, for example, halogen such as chloride, bromide and the like.

The iminothiourea compound of formula (IV) used as a starting material in the above-described conventional preparation method contains a primary amine composed of substituted or unsubstituted phenyl as a reaction leaving group. On the other hand, The compound of formula (2) used as a starting material in the process of the present invention is characterized in that it contains ammonia, a secondary amine and an alcohol as a reaction leaving group.

In the preparation method of the present invention, the compound of formula (1), which is the desired compound, can be prepared by reacting the compound of formula (2) with a compound of formula (3) in a solvent in the presence of a base.

Scheme 2

Examples of the reaction solvent include alcohol compounds such as methanol, ethanol and isopropyl alcohol; Aromatic hydrocarbon compounds such as benzene, toluene and xylene; Ether compounds such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran; Ketone compounds such as acetone, methyl ethyl ketone, and cyclohexanone; Nitrile compounds such as acetonitrile and propionitrile; Halogenated hydrocarbon compounds such as dichloromethane, 1,2-dichloroethane, and cryptole; Ester compounds such as methyl acetate and ethyl acetate; N, N-dimethylformamide, N, N-dimethylacetamide, dimethylsulfoxide and the like can be used. Among them, toluene which is an aromatic hydrocarbon compound is particularly preferable.

The base used in the production method of the present invention can be obtained by reacting an organic base such as triethylamine, tributylamine, diisopropylethylamine, N, N-dimethylaniline, pyridine or 4-dimethylaminopyridine with sodium hydroxide, Potassium, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, or potassium hydride. Of these, organic bases are more preferable. Particularly preferred examples of the organic base include alkyl amines such as triethylamine, tributylamine and diisopropylethylamine. The amount of the base to be used may be 0.2 to 5 equivalents, but is preferably 0.2 to 1 equivalent.

The reaction can be carried out at a temperature of 20 to 120 ° C, and a particularly preferable reaction temperature is 30 to 50 ° C. The reaction time is suitably about 3 hours to 6 hours.

The present invention provides a variety of advantages over conventional processes by using the thiocarbamyl compound of formula (II) as the starting material for the preparation of the compound of formula (I).

First, since the reaction yield is as high as 90 to 95%, the process economy is excellent.

Second, since the reaction can be performed at a relatively low reaction temperature and the reaction time is greatly shortened, desired compound can be produced in a short time under mild conditions.

In addition, when an aromatic hydrocarbon compound such as toluene is used as a preferable reaction solvent, side reactions occurring when an alcohol is used as a solvent as in the prior art can be suppressed.

In addition, when the base is used in an amount of 1.0 equivalent or less, the decomposition of the reactants and products caused by using a large amount of base can be substantially prevented.

On the other hand, each exemplary preparation method according to the substituent type (NH ₂ , NR ⁴ R ⁵ , OR ⁶ ) of R ³ of the thiocarbamyl compound of the formula (2) will be described.

First, the thiocarbamylamidine compound of the following formula (5) wherein R ³ is NR ⁴ R ⁵ in formula (2)

(a) reacting an amide compound of the following formula (6) with a halogenating agent in a solvent to convert it into a Vilsmeier intermediate of the formula (7) (hereinafter abbreviated as step 1);

(b) converting the bisphenol intermediate of formula (7) with ammonia to form an amidine compound of formula (8) (hereinafter abbreviated as step 2); And

(c) reacting an amidine compound of formula (8) with an isothiocyanate compound of formula (9) in the presence of a base to produce a compound of formula (5) (hereinafter abbreviated as step 3);

. ≪ / RTI >

(5)

(5)

(6)

(6)

(7)

(7)

(8)

(8)

R ¹ NCS (9)

In the above formulas, R ¹ , R ² , R ⁴ and R ⁵ are the same as in the formulas (1) and (2).

The reaction process can be represented by the following reaction formula (3).

Scheme 3

Examples of the halogenating agent that can be used in the first step reaction for forming the Vilsmeier intermediate of formula (7) in the above Reaction Scheme 3 include thionyl chloride (SOCl ₂ ), phosgene (COCl ₂ ), phosphorus oxychloride (POCl ₃ ), And the like, and the amount thereof is suitably from 1 to 4 equivalents. The reaction can be carried out in a temperature range of -20 to 80 ° C, preferably -5 to 40 ° C, and a reaction time of 2 to 6 hours is suitable. Examples of the reaction solvent include aromatic hydrocarbon compounds such as benzene, toluene and xylene; Halogenated hydrocarbon compounds such as dichloromethane, 1,2-dichloroethane and chloroform; Ether compounds such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran; Ketone compounds such as acetone, methyl ethyl ketone, and cyclohexanone. Of these, halogenated hydrocarbon compounds such as dichloromethane, 1,2-dichloroethane and chloroform are more preferable. In some cases, N, N-dimethylformamide can be used as a catalyst.

The amount of the ammonia used in the second step reaction is suitably 2 to 8 equivalents. It is appropriate to carry out the reaction at a temperature of -15 to 30 캜 for about 3 hours to 6 hours.

In the reaction of Step 3, the base may be an organic base such as triethylamine, tributylamine, diisopropylethylamine, N, N-dimethylaniline, pyridine or 4-dimethylaminopyridine and an organic base such as sodium hydroxide, Inorganic bases such as lithium hydroxide, calcium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydride and potassium hydride can be used. Preferably, an inorganic base is used, and sodium hydroxide is particularly preferable. The amount of the base to be used is 1.0 to 4 equivalents, preferably 1.0 to 2.0 equivalents. The amount of the isothiocyanate compound of formula (9) is suitably 1 to 2 equivalents, and the reaction can be carried out in the temperature range of 0 to 50 ° C, but it is more preferably performed at 10 to 30 ° C, Hour to 7 hours is suitable.

The thiocarbamylimidate compound of formula (13), wherein R ³ is OR ⁶ in formula (2)

(a) reacting a nitrile compound of the following formula (10) with an alcohol compound of the formula (11) in the presence of hydrochloric acid gas to convert it to an imidate compound of the formula (12) And

(b) reacting the compound of formula (12) with an isothiocyanate compound of formula (9) in the presence of a base to produce a compound of formula (13) (hereinafter abbreviated as a two step reaction);

. ≪ / RTI >

R ² CN (10)

R < ⁶ > OH (11)

(12)

(12)

(13)

(13)

In the above formulas, R ¹ , R ² and R ⁶ are the same as those in formulas (1) and (2).

The above reaction process can be represented by the following reaction formula (4).

Scheme 4

The amount of the hydrochloric acid gas used in the first step reaction is 1 to 5 equivalents, the reaction temperature is suitably -10 to 30 占 폚, and the reaction time is suitably 5 to 15 hours. The alcohol compound of formula (11) substantially acts as a solvent.

In the two-step reaction, the solvent includes aromatic hydrocarbon compounds such as benzene, toluene, and xylene; Halogenated hydrocarbon compounds such as dichloromethane, 1,2-dichloroethane and chloroform; Ether compounds such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran; Ketone compounds such as acetone, methyl ethyl ketone, and cyclohexanone; And ester compounds such as methyl acetate and ethyl acetate. Of these, toluene is particularly preferable. Examples of the base include organic bases such as triethylamine, tributylamine, diisopropylethylamine, N, N-dimethylaniline, pyridine, and 4-dimethylaminopyridine, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, Potassium carbonate, sodium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride and the like. Of these, organic bases are more preferable. The amount of the base to be used is 1.0 to 4 equivalents. The amount of the isothiocyanate compound of formula (9) is suitably from 1 to 2 equivalents. The reaction temperature can be from 10 to 120 캜, and the reaction time is suitably from 2 to 5 hours.

The thiocarbamylamidine compound of formula (15), wherein R ³ is NH ₂ ,

(a) reacting an imidate compound represented by the following formula (12) with an ammonia gas to convert it to an amidine compound represented by the following formula (14) (hereinafter referred to as a 1-step reaction); And

(b) reacting a compound of formula (14) with an isothiocyanate compound of formula (9) in the presence of a base in a solvent to prepare a compound of formula (15) (hereinafter referred to as a two step reaction);

And the like.

(14)

(14)

(15)

(15)

In the above formulas, R ¹ , R ² and R ⁶ are the same as those in formulas (1) and (2).

The reaction process can be represented by the following reaction formula (5).

Scheme 5

In the first step reaction, the amount of the ammonia to be used is suitably 3 to 7 equivalents, the reaction temperature is suitably -15 to 25 ° C, and the reaction time is suitably 1 to 5 hours.

In the two-step reaction, the solvent includes aromatic hydrocarbon compounds such as benzene, toluene, and xylene; Halogenated hydrocarbon compounds such as dichloromethane, 1,2-dichloroethane and chloroform; Ether compounds such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran; Ketone compounds such as acetone, methyl ethyl ketone, and cyclohexanone; Nitrile compounds such as acetonitrile and propionitrile; And ester compounds such as methyl acetate and ethyl acetate. Of these, nitrile compounds are particularly preferable. Examples of the base include organic bases such as triethylamine, tributylamine, diisopropylethylamine, N, N-dimethylaniline, pyridine, and 4-dimethylaminopyridine, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, Potassium carbonate, sodium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride and the like. Of these, inorganic bases are more suitable. The amount of the base to be used is 1.0 to 4 equivalents, preferably 1.0 to 2.0 equivalents. The amount of the isothiocyanate compound of formula (9) is suitably from 1 to 2 equivalents. The reaction temperature can be from 10 to 120 캜, and the reaction time is suitably from 2 to 5 hours.

The synthesis methods described above will be described in more detail in the following Preparation Examples. Representative compounds of Formula 2 according to the present invention are shown in Table 1 below.

Meanwhile, the thiophene acetamide compound of Formula 3 used as another starting material in Reaction Scheme 2 is known from Korean Patent Laid-Open Publication No. 98-40539 and International Patent Application WO 00/18766, The description is not separately described in the specification. Accordingly, the contents of the above applications are incorporated herein by reference.

Hereinafter, the present invention will be described more specifically based on the following examples. However, these examples are intended to illustrate the present invention and in no way should the scope of the present invention be limited to these examples.

Preparation Example 1: Synthesis of 1-ethylthiocarbamyl-2-ethyl-3,3-diethylamidine (Compound 2 of Table 1)

Diethylpropionamide (12.92 g, 0.1 mol) was dissolved in 50 ml of dichloromethane and cooled to 10 <0> C, then phosphorous oxychloride (23 g, 0.15 mol) was added dropwise over 1 hour. After stirring at about 30 ° C for 4 hours and cooling to -10 ° C, ammonia (13.6 g, 0.8 mol) was added dropwise over 4 hours while maintaining below 20 ° C. The resulting white solid was filtered and washed with 1.5 L of dichloromethane. Sodium hydroxide aqueous solution (0.1 mol) was added to the obtained dichloromethane solution, and ethyl isothiocyanate (8.71 g, 0.1 mol) was added dropwise for 1 hour while maintaining the temperature at 10 ° C or lower, followed by stirring at room temperature for 5 hours. The layers were separated, washed with water, and dichloromethane was removed by vacuum distillation. The residue was recrystallized using toluene-hexane and filtered at 10 ° C. After drying, the title compound (18.31 g, 85.0 mmol) as a light yellow solid was obtained in 85% yield.

^{1 H NMR (DMSO- d 6)} : δ 8.40 (0.6H, s), 8.33 (0.4H, s), 3.41 (1.2H, qd,), 3.36 ~ 3.26 (4H, m), 3.04 (0.8H, qd), 2.83 (0.8H, q), 2.60 (1.2H, q), 1.1-0.97 (12H, m)

Production Example 2: Synthesis of 1-ethylthiocarbamyl-2-ethyl-3-methyl-3-phenylamidine (Compound 3 of Table 1)

N-Methyl-N-phenylpropionamide (3.26 g, 20 mmol) was dissolved in 10 ml of dichloromethane, cooled to 10 ° C and phosphorus oxychloride (4.6 g, 30 mmol) was added dropwise over 1 hour. The mixture was stirred at about 30 DEG C for 4 hours, cooled to -10 DEG C, and ammonia (2.72 g, 0.16 mol) was added dropwise over 4 hours while maintaining the temperature below 20 DEG C. [ The resulting white solid was filtered and washed with 0.3 L of dichloromethane. Sodium hydroxide aqueous solution (20 mmol) was added to the obtained dichloromethane solution, and ethyl isothiocyanate (1.74 g, 20 mmol) was added dropwise for 1 hour while maintaining the temperature at 10 ° C or lower, followed by stirring at room temperature for 5 hours. The layers were separated, washed with water, and then dichloromethane was removed by vacuum distillation and then separated by column chromatography to obtain the title compound (1.45 g, 6.7 mmol) in a yield of 34%.

Of the thiocarbamylamidine compounds of the formula (5), the thiocarbamylamidine compounds of the compounds 1 and 4 to 5 exemplified in Table 1 are synthesized similarly to Preparation Example 1.

Production Example 3: Synthesis of 1-ethylthiocarbamyl-2-ethyl-3-ethylimidate (Compound 7 of Table 1)

Propionitrile (1.1 g, 20 mmol) was dissolved in 20 ml of ethanol, hydrochloric acid gas (2.92 g, 80 mmol) was added thereto at 0 ° C for 1 hour and stirred for 10 hours to synthesize imidate hydrochloride. The ethanol solvent was removed by vacuum distillation, and 20 ml of toluene, triethylamine (6.1 g, 60 mmol) and ethyl isothiocyanate (1.92 g, 22 mmol) were charged, and the mixture was heated to reflux for 3 hours. The toluene was removed by vacuum distillation and then separated by column chromatography to obtain the title compound (2.83 g, 15.0 mmol) in 75% yield.

Production Example 4: Synthesis of 1-ethylthiocarbamyl-2-ethylamidine (Compound 6 of Table 1)

Propionitrile (1.1 g, 20 mmol) was dissolved in 20 ml of ethanol. Hydrochloric acid gas (2.92 g, 80 mmol) was added thereto at 0 ° C for 1 hour and stirred for 10 hours to synthesize imidate hydrochloride.

After cooling to -10 DEG C, ammonia (2.04 g, 120 mmol) was added thereto for 1 hour while maintaining the temperature below 20 DEG C, thereby converting it into an amidine compound. The ethanol solvent was removed by vacuum distillation, and 30 ml of acetonitrile, sodium carbonate (4.24 g, 40 mmol) and ethyl isothiocyanate (1.92 g, 22 mmol) were added and the mixture was heated to reflux for 3 hours. The acetonitrile was removed by vacuum distillation and then separated by column chromatography to obtain the title compound (0.86 g, 5.4 mmol) in 27% yield.

Examples of the synthesis of 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide using the compounds in Table 1 are shown in the following examples have.

Synthesis of 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide (1-ethylthiocarbamyl- , 3-diethylamidine (Compound 2 of Table 1)

Ethyl-3,3-diethylamidine (21.54 g, 0.1 mol) and 2-chloro-N- (cyano- 21.47 g, 0.1 mol) and triethylamine (2.02 g, 0.02 mol) were successively added to 200 ml of toluene, and the mixture was stirred at room temperature for 4 hours to complete the reaction. After toluene was removed by vacuum distillation, the mixture was recrystallized from acetone and water and dried to obtain the title compound (30.12 g, 94.0 mmol) in 94% yield.

¹ H NMR (CDCl ₃ ): 隆 7.38 (1H, d), 7.33 (1H, d), 7.04 s, br), 3.26 (2H, q), 2.93 (2H, q), 1.26

Example 2: Synthesis of 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide (1-ethylthiocarbamyl- Methyl-3-phenylamidine (Compound 3 of Table 1)

(2.49 g, 10 mmol) and 2-chloro-N- (cyano-thiophen-2-yl-methyl) -acetamide (2.15 g, 10 mmol) and triethylamine (1.11 g, 11 mmol) were successively added to 20 ml of acetonitrile, followed by stirring at room temperature for 5 hours to complete the reaction. After acetonitrile was removed by vacuum distillation, the mixture was recrystallized from methanol and water and dried to give the title compound (2.88 g, 9 mmol) in 90% yield.

Example 3: Synthesis of 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide (1-ethylthiocarbamyl- (Compound 6 of Table 1)

(1.59 g, 10 mmol) and 2-chloro-N- (cyano-thiophen-2-yl-methyl) -acetamide (2.15 g, 10 mmol) Triethylamine (1.11 g, 11 mmol) was added successively to 20 ml of methanol, and the temperature was raised to 60 ° C and the mixture was stirred for 5 hours. After methanol was removed by vacuum distillation, the mixture was recrystallized from methanol and water and dried to give the title compound (1.09 g, 3.4 mmol) in 34% yield.

Example 4: Synthesis of 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide (1-ethylthiocarbamyl- -Ethylimidate (Compound 7 of Table 1)

Ethyl-imidate (1.88 g, 10 mmol) and 2-chloro-N- (cyano-thiophen-2-yl-methyl) -acetamide (2.15 g, 10 mmol) and triethylamine (1.1 g, 11 mmol) were successively added to 20 ml of toluene, and the mixture was heated to 70 ° C and stirred for 6 hours. The toluene was removed by vacuum distillation, and the mixture was recrystallized from methanol and water and dried to obtain the title compound (17.7 g, 55.2 mmol) in a yield of 55.2%.

In addition, 4-ethyl 2-ethylamino-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) -amide was synthesized using the compounds 1 and 4-5 in Table 1 Are synthesized as described.

INDUSTRIAL APPLICABILITY As described above, according to the production method of the present invention, the compound of the formula (1) can be produced at a high reaction yield in a short period of time under mild conditions using the thiocarbamyl compound (2) as a starting material. Further, by selecting a preferable solvent in the production method of the present invention, the side reaction can be suppressed and the decomposition of the product or the like can be substantially prevented by the preferable amount of the base used.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention based on the above teachings.

Claims (10)

Reacting a thiocarbamyl compound represented by the following formula (2) with a thiopheneacetamide compound represented by the following formula (3) in the presence of a base, wherein the reaction is carried out in the presence of an alcohol compound, an aromatic hydrocarbon compound, an ether compound, a ketone compound, , A halogenated hydrocarbon compound, an ester compound, or a polar solvent, and is carried out at a temperature of 20 to 120 ° C. A process for producing a 2-aminothiazole carboxamide derivative represented by the following formula

(One)

(2)

(3) Wherein R ¹ is C _1-5 linear or branched alkyl, C _1-5 haloalkyl or C _3-6 cycloalkyl; R ² is C _1-3 alkyl or C _1-3 haloalkyl; R ³ is NR ⁴ R ⁵ , In this formula, R ⁴ and R ⁵ independently of one another are C _1-3 alkyl, unsubstituted phenyl, - (CH ₂ ) n- or - (CH ₂ ) ₂ -X- (CH ₂ ) ₂ - Is 4 or 5 and X is O, NH or S; R ⁶ is C _1-3 alkyl; Y is a leaving group. delete The process according to claim 1, wherein the solvent is an aromatic hydrocarbon compound toluene. The method according to claim 1, wherein the base is an organic base or an inorganic base. 5. The process according to claim 4, wherein the base is an organic base. 6. The process according to claim 5, wherein the organic base is an alkylamine. The method according to claim 1, wherein the amount of the base is 0.2 to 5 equivalents. The method according to claim 7, wherein the amount of the base is 0.2 to 1 equivalent. The process according to claim 1, wherein the reaction is carried out for 3 to 6 hours. The method according to claim 1, wherein the reaction temperature is 30 to 50 ° C.