DESC:FIELD
The present disclosure relates to a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds. Particularly, the present disclosure relates to a process for the preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Pyroxasulfone is a pre-emergence herbicide that belongs to the isoxazoline class of herbicides. Pyroxasulfone is used for the control of weeds on wheat, corn, soybean, and the like. Pyroxasulfone particularly controls ‘Phalaris minor’ the major problematic weed encountered in wheat. Pyroxasulfone acts by reducing the biosynthesis of very long-chain fatty acids (VLCFAs) and also builds fatty acid precursors. It provides high efficacy against broadleaf weeds even at low application rates.
4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds are important intermediates used in the production of Pyroxasulfone. Conventional methods for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds are associated with drawbacks such as impurities and a low yield of the product. These conventional processes require further purification which is not economical. The impurities in the final product may affect the efficacy, safety, and stability of the final product. The yield/purity of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds obtained from the known processes is low.
Therefore, there is felt a need to provide a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds that mitigates the aforestated drawbacks or at least provide an alternative solution.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the background or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds.
Yet another object of the present disclosure is to provide a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds with a comparatively better purity and yield.
Still another object of the present disclosure is to provide a simple and cost-effective process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds.
Another object of the present disclosure is to provide an environment-friendly and commercially scalable process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds.
Yet another object of the present disclosure is to provide a process for the preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl) -1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY
A process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound of formula I

I
wherein X is halogen selected from Cl and Br. The process comprises reacting a predetermined amount of 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol with a predetermined amount of halogenating agent optionally in a fluid medium, and optionally in the presence of a catalyst at a predetermined temperature for a predetermined time period to obtain 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The halogenating agent is at least one selected from the group consisting of hydrochloric acid (HCl), thionyl chloride, phosphorous trichloride and hydrobromic acid (HBr).
The fluid medium is acetonitrile (ACN).
The catalyst is at least one selected from the group consisting of benzyl triethyl ammonium chloride, tetrabutylammonium bromide (TBAB), pyridine, picoline, lutidine, quinoline, isoquinoline and dimethylformamide (DMF).
The predetermined temperature is in the range of 20°C to 120°C.
The predetermined time period is in the range of 2 hours to 8 hours.
The mole ratio of 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to the halogenating agent is in the range of 1:1 to 1:6.
The mole ratio of the 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to the catalyst is in the range of 1:0.01 to 1:0.1.
The 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound is at least one selected from the group consisting of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The purity of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound is in the range of 92% to 97%.
DETAILED DESCRIPTION
The present disclosure discloses a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluromethyl)-1H-pyrazole compounds.
Particularly, the present disclosure discloses a process for the preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
Embodiments, of the present disclosure, will now be described herein. Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
The conventional methods for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds are associated with drawbacks such as impurities and a low yield of the product. These conventional processes require further purification which is not economical. The impurities in the final product may affect the efficacy, safety, and stability of the final product. The yield/purity of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds obtained from the known processes is low.
The present disclosure provides an improved process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds.
The process of the present disclosure is simple, environment friendly, economical, and results in improved yield and higher purity of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds, and is commercially scalable.
The process is detailed below:
The process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds comprises reacting (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol with a halogenating agent optionally in a fluid medium, and optionally in the presence of a catalyst at a predetermined temperature for a predetermined time period to obtain 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds.
A schematic representation for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds is given as scheme A:

SCHEME A
In an embodiment of the present disclosure, the halogenating agent is selected from the group consisting of hydrochloric acid (HCl), thionyl chloride, phosphorous trichloride, and hydrobromic acid (HBr). In an exemplary embodiment, the halogenating agent is HCl. In another exemplary embodiment, the halogenating agent is thionyl chloride. In yet another exemplary embodiment, the halogenating agent is hydrobromic acid (HBr).
In an embodiment of the present disclosure, the fluid medium is acetonitrile (ACN).
In an embodiment of the present disclosure, the catalyst is selected from a group consisting of benzyl triethyl ammonium chloride, tetrabutylammonium bromide (TBAB), pyridine, picoline, lutidine, quinoline, isoquinoline and dimethylformamide (DMF). In an exemplary embodiment, the catalyst used is benzyl triethyl ammonium chloride. In another exemplary embodiment, the catalyst is tetrabutyl ammonium bromide (TBAB). In yet another exemplary embodiment, the catalyst is dimethylformamide (DMF). In still another embodiment, the catalyst is pyridine.
In an embodiment of the present disclosure, the predetermined temperature is in the range of 10 °C to 120 °C. In an exemplary embodiment, the predetermined temperature is 100 °C. In another exemplary embodiment, the predetermined temperature is 30 °C.
In an embodiment of the present disclosure, the predetermined time period is in the range of 1 hour to 8 hours. In an exemplary embodiment, the predetermined time period is 6 hours. In another exemplary embodiment, the predetermined time period is 7 hours. In yet another exemplary embodiment, the predetermined time period is 2 hours 30 minutes.
In an embodiment of the present disclosure, the predetermined mole ratio of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to the halogenating agent is in the range of 1:1 to 1:6. In an exemplary embodiment, the predetermined mole ratio is 1:5. In another exemplary embodiment, the predetermined mole ratio is 1:1.1.
In an embodiment of the present disclosure, the predetermined mole ratio of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to the catalyst is in the range of 1:0.01 to 1:0.1. In an exemplary embodiment, the predetermined ratio of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to the catalyst is 1:0.1.
In an embodiment of the present disclosure, 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds is selected from 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
In an embodiment of the present disclosure, the 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound have a purity of greater than 80%. In an exemplary embodiment, the yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole is 85% and the purity is greater than 95%. In another exemplary embodiment, the yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole is 93% and the purity is greater than 92%. In yet another exemplary embodiment, the yield of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole is 92.7% and the purity is greater than 95%.
The present disclosure provides a simple and economical process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds with a comparatively higher yield and better purity.
The foregoing description of the embodiments has been provided for purposes of illustration and is not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments are scalable to industrial/commercial process.
EXPERIMENTAL DETAILS
EXAMPLE 1: Preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 530 ml (5 moles) of aqueous HCl (30%) and 22.8 gm (0.1 moles) of benzyl triethyl ammonium chloride to obtain a mixture. The mixture was heated to 100°C to 105°C and was further maintained at 100°C for 6 hours to obtain a product mixture. The reaction was monitored by HPLC.
The product mixture was cooled to 30°C to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer was separated from the biphasic mixture and washed with 100 ml of 10% aqueous sodium chloride, followed by drying over magnesium sulphate and concentrated to obtain 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 85% and the purity was >95%.
EXAMPLE 2: Preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 530 ml (5 moles) of aqueous HCl (30%) and 32.2 gm (0.1 moles) of tetrabutylammonium bromide (TBAB) to obtain a mixture. The mixture was heated to 100°C to 105°C and was further maintained at 100°C for 7 hours to obtain a product mixture. The reaction was monitored by HPLC.
The product mixture was cooled to 30°C to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer was separated from the biphasic mixture and washed with 100 ml of 10% aqueous sodium chloride, followed by drying over magnesium sulphate and concentrated to obtain 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 93% and the purity was >92%.
EXAMPLE 3: Preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 530 ml (5 moles) of aqueous HCl (30%) to obtain a mixture. The mixture was heated to 100°C to 105°C and was further maintained at 100°C for 2 hours 30 minutes to obtain a product mixture. The reaction was monitored by HPLC.
The product mixture was cooled to 30°C to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer was separated from the biphasic mixture and washed with 100 ml of 10% aqueous sodium chloride, followed by drying over magnesium sulphate and concentrated to obtain 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 85% and the purity was >95%.
EXAMPLE 4: Preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 150 ml of acetonitrile and 2 ml of pyridine to obtain a mixture. To the mixture, 79.8ml (1.1 moles) of thionyl chloride was slowly added at 20°C to 25°C and was maintained at 30°C (temperature was raised due exothermic reaction after addition of thionyl chloride) for 8 hours to obtain a reaction mixture. The reaction was monitored by HPLC.
The reaction mixture was concentrated under vacuum to remove excess thionyl chloride and obtain a product mixture. To the product mixture, 200 ml of methylene dichloride (MDC) and 100 ml of water were added to obtain a first biphasic mixture comprising a first organic layer (MDC) and a first aqueous layer. The first organic layer was separated from the first biphasic mixture and the remaining first aqueous layer, was further extracted with 100 ml of methylene dichloride to obtain a second biphasic mixture comprising a second organic layer and a second aqueous layer. Methylene dichloride layer (second organic layer) with 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was separated. The so obtained organic layers (first and second) were combined and dried over magnesium sulphate followed by concentrating to remove the methylene dichloride under reduced pressure to obtain 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 93% and the purity was >82%.
EXAMPLE 5: Preparation of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 150 ml of acetonitrile and 2 ml of dimethylformamide (DMF) to obtain a mixture. To the mixture, 79.8 ml (1.1 moles) of thionyl chloride was slowly added at 20°C to 25°C and was maintained at 30°C for 7 hours to obtain a reaction mixture. The reaction was monitored by HPLC.
The reaction mixture was concentrated under vacuum to remove excess thionyl chloride to obtain a product mixture. To the product mixture, 200 ml of methylene dichloride (MDC) and 100 ml of water were added to obtain a first biphasic mixture comprising a first organic layer (MDC) and a first aqueous layer. The first organic layer was separated from the first biphasic mixture, and the remaining first aqueous layer, was further extracted with 100 ml of methylene dichloride to obtain a second biphasic mixture comprising a second organic layer and a second aqueous layer. The second organic layer of Methylene dichloride layer (MDC) containing 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was separated. The so obtained organic layers (MDC layers- first and second layers) were combined and dried over magnesium sulphate followed by concentrating to remove the methylene dichloride (MDC) under reduced pressure to obtain 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 88% and the purity was >84%.
EXAMPLE 6: Preparation of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 566.0 ml (5 moles) of aqueous HBr (48%) and 22.8 gm (0.1 moles) of benzyl triethyl ammonium chloride to obtain a mixture. The mixture was heated to 100°C to 105°C and was further maintained at 100°C for 6 hours to obtain a product mixture. The reaction was monitored by HPLC.
The product mixture was cooled to 30°C to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer was separated from the biphasic mixture and washed with 100ml of 10% aqueous sodium chloride, followed by drying over magnesium sulphate and concentrated to obtain 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 92.7% and the purity was >95%.
EXAMPLE 7: Preparation of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole in accordance with present disclosure
246 gm (1 mole) of (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol was charged into a reactor followed by adding 566.0 ml (5 moles) of aqueous HBr (48%) to obtain a mixture. The mixture was heated to 100°C to 105°C and was further maintained at 100°C for 2 hours 30 minutes to obtain a product mixture. The reaction was monitored by HPLC.
The product mixture was cooled to 30°C to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer was separated from the biphasic mixture and washed with 100 ml of 10% aqueous sodium chloride, followed by drying over magnesium sulphate and concentrated to obtain 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.
The yield of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole was 85% and the purity was >95%.
TECHNICAL ADVANCEMENT
The present disclosure described hereinabove has several technical advantages including, but not limited to, the realization of a process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds that
• proceeds under mild reaction conditions;
• is a simple and environment friendly process; and
• provides 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compounds having a comparatively high purity and high yield.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Variations or modifications to the formulation of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values given for various physical parameters, dimensions, and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions, and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,CLAIMS:WE CLAIM:
1. A process for the preparation of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound of formula I

formula I
wherein X is halogen selected from Cl and Br,
said process comprising reacting a predetermined amount of 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol with a predetermined amount of halogenating agent optionally in a fluid medium, and optionally in the presence of a catalyst at a predetermined temperature for a predetermined time period to obtain 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.

2. The process as claimed in claim 1, wherein said halogenating agent is selected from the group consisting of hydrochloric acid (HCl), thionyl chloride, phosphorous trichloride, and hydrobromic acid (HBr).

3. The process as claimed in claim 1, wherein said fluid medium is acetonitrile (ACN).

4. The process as claimed in claim 1, wherein said catalyst is at least one selected from the group consisting of benzyl triethyl ammonium chloride, tetrabutylammonium bromide (TBAB), pyridine, picoline, lutidine, quinoline, isoquinoline and dimethylformamide (DMF).

5. The process as claimed in claim 1, wherein said predetermined temperature is in the range of 20°C to 120°C.

6. The process as claimed in claim 1, wherein said predetermined time period is in the range of 2 hours to 8 hours.

7. The process as claimed in claim 1, wherein the mole ratio of 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to said halogenating agent is in the range of 1:1 to 1:6.

8. The process as claimed in claim 1, wherein the mole ratio of 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methanol to said catalyst is in the range of 1:0.01 to 1:0.1.

9. The process as claimed in claim 1, wherein said 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound is at least one selected from the group consisting of 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole and 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole.

10. The process as claimed in claim 1, wherein the purity of 4-(halomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole compound is in the range of 92% to 97%.

Dated this 22nd day of March, 2024

_______________________________
MOHAN RAJKUMAR DEWAN, IN/PA – 25
OF R. K. DEWAN & CO.
AUTHORIZED AGENT OF APPLICANT

TO,
THE CONTROLLER OF PATENTS
THE PATENT OFFICE, AT MUMBAI