CN115806497A - Improved process for preparing anthranilate compounds - Google Patents
Improved process for preparing anthranilate compounds Download PDFInfo
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- CN115806497A CN115806497A CN202211133938.1A CN202211133938A CN115806497A CN 115806497 A CN115806497 A CN 115806497A CN 202211133938 A CN202211133938 A CN 202211133938A CN 115806497 A CN115806497 A CN 115806497A
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Abstract
The present invention relates to an improved process for the preparation of anthranilate compounds. The present invention relates in particular to a process for the preparation of a compound of formula (I) comprising: i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV); and ii) reacting the obtained compound of formula (IV) with sulfuryl chloride to obtain the compound of formula (I). The method is simple, cost effective and industrially feasible; there is no need to separate the compound of formula (IV), thereby reducing effluent generation and process steps;use of cost effective reagents such as sulfuryl chloride; and the platinum catalyst used for reducing the compound of formula (II) can be recycled many times.
Description
Technical Field
The present invention relates to an improved process for the preparation of ortho amino acid benzoate compounds of formula (I),
background
Anthranilates are versatile and inexpensive starting materials/intermediates for the preparation of many pharmaceutical and agricultural products.
Anthranilates are known to be useful in the preparation of an important class of synthetic insecticides, namely diamides. Diamide pesticide molecules have the same target site, the ryanodine receptor, and are classified in group 28 of the Insecticide Resistance Action Committee (IRAC) mode of action categories, the ryanodine receptor modulators. Diamides such as chlorantraniliprole, cyantraniliprole, cyclobenzamide, tetrachlorobenzamide and tetraphenyl formamide are well known and have high efficacy.
Various synthetic routes to bisamide insecticides have been disclosed in the prior art, and many have been carried out by anthranilate compounds of formula (I).
Methods for preparing intermediates, i.e., anthranilates of formula (I), are known in the art. However, the reaction sequence disclosed in the prior art is cumbersome to perform and not suitable for commercial production. Some of these methods involve the use of expensive chlorinating agents such as sodium hypochlorite solutions, N-chlorosuccinimide, and the like. The use of such expensive reagents on a large scale is economically unfeasible.
WO2006062978 discloses a process for the preparation of anthranilate compounds of formula (I) by chlorination of methyl 2-amino-3-methylbenzoate with sulfuryl chloride in acetonitrile. The process comprises adding a small amount of sulfuryl chloride within 3-3.5 hours, maintaining the temperature at 50-55 ℃, then immediately cooling to 5 ℃, and then performing a post-treatment procedure. The limitations of this process, which requires very slow addition of sulfuryl chloride followed by immediate cooling to 5 ℃, are pointed out. In addition, the solvent used for the reaction is acetonitrile, which is hygroscopic and may lead to an increase in the water content of the reaction mixture. It is well known that sulfuryl chloride reacts readily with water, potentially forming gaseous by-products in the form of sulfur oxides, and that the formation of such gaseous by-products may continue as the reaction proceeds. In large scale production, gas evolution is very abundant and at any unpredictable time it can occur in the form of sudden surges, leading to a situation like a runaway reaction, resulting in reactants being thrown out of the reactor. These limitations and the problems associated with this approach make this approach cumbersome, inefficient, and dangerous on a commercial scale.
Therefore, there is a need to find a safe method to perform the reaction on a commercial scale and to overcome one or more of the problems associated with the prior art.
Disclosure of Invention
It is an object of the present invention to provide a process for preparing anthranilate compounds of formula (I).
It is another object of the present invention to provide an improved, cost-effective and industrially feasible process for the preparation of anthranilate compounds of formula (I).
It is another object of the present invention to provide a process for preparing anthranilate compounds of formula (I) that does not require extreme temperature conditions and complicated post-treatment steps.
According to one aspect of the present invention, there is provided a process for the preparation of a compound of formula (I) without isolation of the compound of formula (IV).
According to another aspect of the present invention, there is provided a process for preparing an ortho-amino acid formate compound of formula (I),
the method comprises the following steps:
a) Methylating a compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
b) Extracting the compound of formula (IV) with a chlorine-containing solvent; and treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
according to another aspect of the present invention, there is provided a process for preparing an anthranilate compound of formula (I),
the method comprises the following steps:
a) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
b) Treating the compound of formula (IV) with a chlorine-containing solvent and treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) used in step a) is prepared by reducing a compound of formula (II),
according to still another aspect of the present invention, there is provided a process for preparing an orthocarbamate compound of formula (I),
the method comprises the following steps:
a) Methylating a compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
b) Extracting the compound of formula (IV) with a chlorine-containing solvent, treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) used in step a) is prepared by reducing a compound of formula (II) in the presence of a platinum catalyst,
Detailed Description
The following description is provided to facilitate a thorough understanding of exemplary embodiments of the invention. It includes various specific details that are helpful in understanding, but these are to be considered exemplary only. The invention also includes all of the steps, features, compositions and methods referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features.
Definition of
For convenience, certain terms, examples, and alternatives used in the specification are described herein before further description of the invention. These definitions should be read in light of the remainder of this disclosure and understood by those skilled in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The terms used in the present specification are defined as follows unless otherwise limited in specific cases.
The term "room temperature" essentially means a temperature in the range of 20-35 ℃ unless otherwise stated.
The term "purity" means purity as determined by HPLC ("high performance liquid chromatography").
As used herein, the term "about" or "approximately" encompasses the stated value and is intended to encompass the measurement and the error associated with measurement of the particular quantity (i.e., the limitations of the measurement system), within an acceptable range of deviation of the particular value as determined by one of ordinary skill in the art. For example, "about" may mean within one or more standard deviations, or within ± 10 or ± 5 of the stated value. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The endpoints of all ranges are inclusive of the range and independently combinable. It is understood that where a parameter range is provided, all integers within the range and tenths thereof are also provided. For example, "0.1-80%" includes 0.1%, 0.2%, 0.3%, etc., up to 80%. As used herein, the terms "comprising," "including," "having," "containing," "involving," and the like are to be construed as open-ended, i.e., meaning including, but not limited to.
The terms "preferred" and "preferably" refer to embodiments of the invention that may provide certain benefits under certain circumstances. In one embodiment, the aspects and embodiments described herein should also be construed as the expression "comprising" instead of "consisting of 8230; or" consisting essentially of 8230; or "consisting of 8230, to name a few.
An improved process for the preparation of anthranilate compounds of formula (I) is described. The process of the present invention is based on a novel reaction sequence which can be easily implemented in large-scale production to provide the desired compound in high yield, but without involving any risk of liberating the violent gaseous by-products that arise from the use of sulfuryl chloride. Therefore, the method provided by the invention is economical, environment-friendly and safe.
According to one aspect of the present invention, there is provided a process for the preparation of an anthranilate compound of formula (I) without the need for isolation of the compound of formula (IV),
in one embodiment, there is provided a process for the preparation of anthranilates of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV); and
ii) treating the compound of formula (IV) with sulfuryl chloride to obtain an anthranilate of formula (I),
wherein the process is carried out without isolating the compound of formula (IV).
In one embodiment, the methylating agent used is selected from methyl iodide, dimethyl carbonate, dimethyl sulfate, diazomethane, dimethoxypropane, dimethyl zinc, methyl fluorosulfonate, methyl trifluoromethanesulfonate and the like, preferably dimethyl sulfate is used.
The amount of methylating agent used is from 1 to 3 moles with respect to the compound of formula (III).
In one embodiment, the methylation is carried out in the presence of a solvent.
The solvent used is selected from organic solvents such as dichloromethane, dichloroethane, acetonitrile, dimethylformamide, dimethylacetamide, N-methylpyrrolidone and mixtures thereof.
In one embodiment, the methylation reaction is carried out in the presence of dimethylformamide as a solvent.
In one embodiment, the methylation reaction is carried out in the presence of dimethylacetamide as a solvent.
The amount of solvent used relative to the compound of formula (III) is about 4 to 10 times.
In one embodiment, the methylation reaction is carried out in the presence of a base.
Typically, the base used is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and the like.
The amount of base used is 1 to 1.5 moles with respect to the compound of formula (III).
In one embodiment, the methylation reaction is carried out at a temperature in the range of from 20 to 100 ℃.
In one embodiment, the methylation reaction is carried out for 0.5 to 6 hours.
In one embodiment, step i) of the process further comprises isolating the compound of formula (IV) with a chlorine-containing solvent and reducing the moisture content of the organic layer to less than 0.5% w/w.
In one embodiment, the chlorine-containing solvent used is selected from the group consisting of dichloromethane, dichloroethane, chloroform, 1, 2-trichloroethane, chlorobenzene, o-dichlorobenzene, and the like.
In one embodiment, the chlorine-containing solvent used is dichloroethane.
The amount of the chlorine-containing solvent used is about 3 to 10 times relative to the compound of formula (III).
In one embodiment, the moisture content of the organic layer is reduced to less than 0.5%.
In one embodiment, the compound of formula (IV) obtained in step i) is not isolated and the organic layer obtained in step i) is directly used in step ii) for further processing.
In one embodiment, the compound of formula (IV) obtained in step i) may be isolated by conventionally known methods such as distillation, precipitation, etc., and then directly used in step ii).
In one embodiment, in step ii), the amount of sulfuryl chloride used is 0.5 to 1.5 moles with respect to the compound of formula (III).
In one embodiment, the sulfuryl chloride treatment is carried out at a temperature of 20 ℃ to 100 ℃. In one embodiment, the sulfuryl chloride treatment is carried out at a temperature of 40 ℃ to 70 ℃.
In one embodiment, the treatment with sulfuryl chloride is carried out for 10 minutes to 3 hours.
According to another aspect of the present invention, there is provided a process for the preparation of anthranilate compounds of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
ii) isolating the compound of formula (IV) by treatment with a chlorine-containing organic solvent; and further treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
in one embodiment, the chlorine-containing solvent used is selected from the group consisting of dichloromethane, dichloroethane, chloroform, 1, 2-trichloroethane, chlorobenzene, o-dichlorobenzene, and the like.
In one embodiment, the chlorine-containing solvent used is dichloroethane.
The amount of chlorine-containing solvent used relative to the compound of formula (III) is about 3 to 10 times.
In one embodiment, step ii) of the method further comprises reducing the moisture content of the organic layer to less than 0.5% w/w prior to treatment with sulfuryl chloride.
In one embodiment, the moisture content of the organic layer is reduced by azeotropic distillation.
In one embodiment, the moisture content is reduced to less than 0.5%.
Preferably, the moisture content of the organic layer is adjusted to less than 0.1% w/w.
In one embodiment, the sulfuryl chloride is used in an amount of 0.5 to 1.5 moles with respect to the compound of formula (III).
In one embodiment, step ii) is performed in the presence of a catalyst. Preferably, the catalyst used is dimethylformamide.
In one embodiment, the sulfuryl chloride treatment is carried out at a temperature of 20 ℃ to 100 ℃. In one embodiment, the sulfuryl chloride treatment is carried out at a temperature of 40 ℃ to 70 ℃.
In one embodiment, the treatment with sulfuryl chloride is carried out for 10 minutes to 3 hours.
The present inventors have skillfully designed the process of the present invention by carefully selecting the solvent used in the process of the present invention, which is not hygroscopic in nature. The use of such solvents allows the moisture content to be adjusted to a large extent.
Furthermore, by extracting the compound of formula (IV) using a chlorine-containing organic solvent, the use of multiple solvents in the process can also be avoided. In general, the organic layer after adjusting the moisture content can be directly used for chlorination reaction without isolating the compound of formula (IV), thereby making the process efficient, environmentally friendly and economical for large-scale production.
Also, since there is no need to isolate the compound of formula (IV), the possibility of yield loss due to solid handling steps such as crystallization or precipitation or filtration is reduced.
According to one embodiment of the invention, the compound of formula (III) is prepared by reduction of a compound of formula (II),
in one embodiment, the step of reducing the compound of formula (II) to the compound of formula (III) is carried out in the presence of a catalyst and a solvent.
Typically, the catalyst used is selected from palladium catalysts, platinum catalysts or raney nickel. Palladium or platinum catalysts, such as palladium on carbon or platinum on carbon, may be used. Preferably, a platinum catalyst is used.
In one embodiment, the platinum catalyst used in the step of reducing the compound of formula (II) to the compound of formula (III) may be recycled and reused for the same reaction more than 20 times, thereby making the process cost-effective and economically viable on an industrial scale.
In one embodiment, the solvent used in the step of reducing the compound of formula (II) to the compound of formula (III) is selected from nitriles (e.g., acetonitrile) or C1-C5 alcohols (e.g., methanol, ethanol, isopropanol, n-propanol, butanol, tert-butanol) and the like.
In one embodiment, the step of reducing the compound of formula (II) to the compound of formula (III) is carried out at a temperature of from 20 to 80 ℃.
In one embodiment, the step of reducing the compound of formula (II) to the compound of formula (III) is performed for 1 to 10 hours.
According to another aspect of the present invention, there is provided a process for preparing an anthranilate compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
ii) extracting the compound of formula (IV) in a chlorine-containing organic solvent and treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) used in step i) is prepared by reduction of a compound of formula (II),
according to yet another aspect of the present invention, there is provided a process for preparing an anthranilate compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
ii) extracting the compound of formula (IV) with a chlorine-containing organic solvent and treating the separated organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) used in step i) is prepared by reducing a compound of formula (II) in the presence of a platinum catalyst,
according to one aspect of the present invention, there is provided a process for preparing an anthranilate compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
ii) extracting the compound of formula (IV) in a chlorine-containing organic solvent to reduce the water content of the organic layer to less than 0.5% w/w;
iii) Treating the organic layer with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) used in step i) is prepared by reduction of a compound of formula (II),
according to yet another aspect of the present invention, there is provided a process for preparing an anthranilate compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain an ester of formula (IV),
ii) extracting the ester of formula (IV) in a chlorine-containing solvent to obtain an organic layer;
iii) Reducing the moisture content of the organic layer to less than 0.5%;
iv) treating the organic layer of step c) with sulfuryl chloride to obtain an anthranilate compound of formula (I),
wherein the compound of formula (III) is prepared by reducing a compound of formula (II) in the presence of a platinum catalyst,
in one embodiment, the compounds of formula (I) may be used to prepare diamide insecticidal compounds, such as chlorantraniliprole, cyantraniliprole, cyclobenzamide, tetrachlorobenzamide, and tetraphenyl formamide. Preferably, the compound of formula (I) is used for the preparation of chlorantraniliprole.
The invention has the following advantages: 1. the process is a simple, cost effective and industrially feasible process for the preparation of anthranilate compounds of formula (I). 2. The process does not require the isolation of the compound of formula (IV), thereby reducing effluent generation and handling steps. 3. Involving the use of cost-effective reagents such as sulfuryl chloride. 4. The platinum catalyst used for the reduction of the compound of formula (II) can be recycled many times.
Examples
The process of the present invention for preparing anthranilate compounds of formula (I) can be determined by the experiments exemplified below. These examples are merely illustrative and should not be construed as limiting the scope and underlying principles of the invention in any way. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the following examples and the foregoing description.
Details of the analysis method：
Samples were analyzed on a high performance liquid chromatograph equipped with a UV detector using a COSMOSIL-5C18-MS-II column.
Example 1 preparation of 2-nitro-3-methylbenzoic acid-compound of formula (II)
6147g of fuming nitric acid were charged into the reaction vessel and cooled to-15 to-10 ℃ before 1639g of m-toluic acid was added and the reaction mixture was maintained at the same temperature for 2 hours. After the reaction was completed, crude 2-nitro-3-methylbenzoic acid was separated, and 1180g of 50% ethanol was added. The mixture was heated to 75-80 ℃ for 1 hour, then cooled to room temperature, and the product was filtered and dried to obtain 1000g of 2-nitro-3-methylbenzoic acid.
Example 2 preparation of 2-amino-3-methylbenzoic acid-compound of formula (III)
1032g of 2-nitro-3-methylbenzoic acid, 51g of a 3 wt% platinum on activated carbon (Pt/C) catalyst and 6640g of methanol were added to the reaction vessel. Mixing the mixture at 30 deg.C at a concentration of 4-6kg/cm 2 The hydrogenation was carried out and then the temperature of the reaction mixture was raised to 50-55 ℃ and maintained at this temperature for 6 hours. After completion of the reaction, the reaction mixture was filtered to recover the catalyst, and the filtrate was distilled to recover about 70% of the used solvent and obtain a reaction mass. Then, 1674g of water was added, and the mixture was held at 20 to 25 ℃ for 1 hour to precipitate the product. The product was filtered and dried to obtain 806g of 2-amino-3-methylbenzoic acid.
Example 3: preparation of methyl 3-methyl-2-aminobenzoate-Compounds of formula (IV)
To a mixture of 5250g of dimethylformamide and 806g of 2-amino-3-methylbenzoic acid, 850g of potassium carbonate was added and the reaction mixture was heated to 50-55 ℃. Keeping the temperature to 50-55 ℃, adding 1380g of dimethyl sulfate within 2-3 hours, and heating to 65-70 ℃. The mixture is held at this temperature for 3 to 4 hours. After completion of the reaction, the solvent used was distilled off, and 4050g of dichloroethane was added to the residue thus obtained. Then 4850g of water was added to the mixture, and the mixture was stirred at room temperature for 1 hour. After 1 hour, the layers were separated and the organic layer was azeotropically distilled under vacuum of 550-650mmHg at 50-55 deg.C. The moisture content of the organic layer was reduced to 0.1% or less, and the organic layer containing 3-methyl-2-aminobenzoate was used in example 4.
Example 4: preparation of 3-methyl-2-amino-5-chlorobenzoic acid methyl ester-compound of formula (I)
660mg of sulfuryl chloride was added to the organic layer obtained in example 3 at 50 to 55 ℃ over 2 to 3 hours, and the reaction was maintained for 1 hour. After completion of the reaction, the mixture was cooled to room temperature, 1200g of water was added, and then 920g of sodium hydroxide was added to adjust the pH to between 5.5 and 6. The layers were separated and the organic layer was distilled off to obtain 1000g of methyl 3-methyl-2-amino-5-chlorobenzoate.
Example 5: preparation of 3-methyl-2-amino-5-chlorobenzoic acid methyl ester-compound of formula (I)
Step 1: preparation of 2-nitro-3-methylbenzoic acid
735g of fuming nitric acid was charged to the reaction vessel and cooled to-15 to-10 ℃. Then 250g of m-toluic acid were added stepwise and the reaction mixture was kept at the same temperature for 2 hours. After completion of the reaction, crude 2-nitro-3-methylbenzoic acid was separated, and 225g of 50% ethanol was added thereto. The mixture was heated to 75-80 ℃ for 1 hour, then cooled to room temperature, and the product was filtered and dried to obtain 161g of 2-nitro-3-methylbenzoic acid.
And 2, step: preparation of 2-amino-3-methylbenzoic acid
159g of 2-nitro-3-methylbenzoic acid, 7g of a 3 wt% platinum on activated carbon (Pt/C) catalyst and 1000g of methanol were charged to a reaction vessel. Mixing the mixture at 30 deg.C at a concentration of 4-6kg/cm 2 The hydrogenation was carried out and the temperature of the reaction mixture was then raised to 50-55 ℃ and maintained at this temperature for 6 hours. After completion of the reaction, the reaction mixture was filtered to recover the catalyst, and the filtrate was distilled to recover about 70% of the used solvent and obtain a reaction mass. To the reaction mass 525g of water were added and the mixture was kept at 20-25 ℃ for 1 hour to precipitate the product. The product was filtered and dried to obtain 120g of 2-amino-3-methylbenzoic acid.
And step 3: preparation of methyl 3-methyl-2-aminobenzoate
To a mixture of 650g of dimethylformamide and 100g of 2-amino-3-methylbenzoic acid from step 2 was added 106g of potassium carbonate, and the resulting reaction mixture was heated to 50-55 ℃. The temperature is kept between 50 and 55 ℃, 170g of dimethyl sulfate is added within 2 to 3 hours, and the temperature is raised to between 65 and 70 ℃. The mixture is held at this temperature for 3 to 4 hours. After the reaction was completed, the solvent used was distilled off, and 600g of water was added. Then, 500g of dichloroethane was added to the mixture, and the mixture was stirred at room temperature for 1 hour. After 1 hour, the layers were separated and the organic layer was azeotropically distilled under vacuum of 550-650mmHg at 50-55 deg.C. The moisture content of the organic layer is reduced to 0.1% or less, and the organic layer containing 3-methyl-2-aminobenzoate is used in step 4.
And 4, step 4: preparation of methyl 3-methyl-2-amino-5-chlorobenzoate
82g of sulfuryl chloride was added to the organic layer obtained in step 3 at 50 to 55 ℃ over 2 to 3 hours, and the reaction was maintained for 1 hour. After completion of the reaction, the mixture was cooled to room temperature, 150g of water was added, and then 114g of sodium hydroxide was added to adjust the pH to 5.5 to 6. The layers were separated and the organic layer was distilled off to obtain 124g of methyl 3-methyl-2-amino-5-chlorobenzoate.
Example 6: preparation of methyl 3-methyl-2-amino-5-chlorobenzoate-compound of formula (I) step 1 and step 2 were carried out in a similar manner to example 5.
And step 3: preparation of methyl 3-methyl-2-aminobenzoate
To a mixture of 650g of dimethylformamide and 100g of 2-amino-3-methylbenzoic acid, 106g of potassium carbonate were added and the resulting reaction mixture was heated to 50-55 ℃. 170g of dimethyl sulfate are added to the mixture over 2-3 hours, and the temperature is raised to 65-70 ℃. The mixture is held at this temperature for 3 to 4 hours. After the reaction was completed, the solvent used was distilled off, and then 580g of dichloroethane and 580g of water were added. The mixture is stirred and heated to a temperature of 40-45 ℃. Separating the layers, and distilling the organic layer under 550-650mmHg vacuum at 50-55 deg.C. The moisture content of the organic layer is reduced to 0.1% or less, and the organic layer containing 3-methyl-2-aminobenzoate is used in step 4.
And 4, step 4: preparation of methyl 3-methyl-2-amino-5-chlorobenzoate
82g of sulfuryl chloride and 1g of dimethylformamide were added to the organic layer obtained in step 3 at 50 to 55 ℃ over 2 to 3 hours. The reaction mixture was then kept at the same temperature for 1-2 hours. After completion of the reaction, the mixture was cooled to room temperature, 150g of water was added, and then 50% aqueous sodium hydroxide solution was added to adjust the pH to 5.5 to 6. The layers were separated and the organic layer was distilled off to obtain 124g of methyl 3-methyl-2-amino-5-chlorobenzoate with an HPLC purity of 99.21%.
Claims (14)
1. A process for the preparation of a compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV); and
ii) reacting the compound of formula (IV) obtained with sulfuryl chloride to obtain a compound of formula (I),
2. the process of claim 1, wherein the process is carried out without isolating the compound of formula (IV).
3. The method of claim 1, wherein the methylating agent is selected from the group consisting of: methyl iodide, dimethyl carbonate, dimethyl sulfate, diazomethane, dimethoxypropane, dimethyl zinc, methyl fluorosulfonate and methyl trifluoromethanesulfonate.
4. The method of claim 1, wherein the methylation is carried out in the presence of a solvent.
5. The method of claim 4, wherein the solvent is selected from the group consisting of: dichloromethane, dichloroethane, acetonitrile, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and mixtures thereof.
6. The method of claim 1, wherein the methylation is performed in the presence of a base.
7. The method of claim 6, wherein the base is selected from the group consisting of: sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.
8. The method of claim 1, wherein step i) further comprises isolating the compound of formula (IV) in a chlorine-containing solvent and reducing the moisture content of the organic layer to less than 0.5% w/w.
9. The method of claim 8, wherein the chlorine-containing solvent is selected from the group consisting of: dichloromethane, dichloroethane, chloroform, 1, 2-trichloroethane, chlorobenzene and o-dichlorobenzene.
10. A process according to claim 1, wherein the compound of formula (III) is prepared by reduction of a compound of formula (II),
wherein the reduction of the compound of formula (II) is carried out in the presence of a catalyst and a solvent.
11. The process of claim 10, wherein the catalyst is a metal catalyst selected from the group consisting of palladium, platinum, and raney nickel.
12. The method of claim 10, wherein the catalyst is platinum.
13. The method of claim 10, wherein the solvent is selected from nitriles or C 1 -C 5 An alcohol.
14. A process for the preparation of a compound of formula (I),
the method comprises the following steps:
i) Methylating the compound of formula (III) with a methylating agent to obtain a compound of formula (IV),
ii) treating the compound of formula (IV) with a chlorine-containing solvent to obtain an organic layer;
iii) Reducing the moisture content of the organic layer to less than 0.5%;
IV) treating the compound of formula (IV) with sulfuryl chloride to obtain the compound of formula (I),
wherein the compound of formula (III) is prepared by reducing a compound of formula (II) in the presence of a platinum catalyst,
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| IN202121041920 | 2021-09-16 | ||
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| BR (1) | BR102022018672A2 (en) |
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