Process for preparation of fluxametamide

Abstract

The present invention relates to an improved process for the preparation of isoxazoline- substituted benzamide compound. More particularly, the present invention relates to process for the preparation of Fluxametamide of Formula (I). Further, the present invention relates to an agrochemical composition, wherein the composition comprises at least a bio-active effective amount of Fluxametamide of formula (I) as obtained by the process disclosed in present invention. Furthermore, the present invention also relates to a process for preparing the agrochemical composition comprising Fluxametamide of formula (I) of the present invention.

Description

[0001] PROCESS FOR PREPARATION OF FLUXAMETAMIDE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to an improved process for the preparation of isoxazolinesubstituted benzamide compound. More particularly, the present invention relates to process for the preparation of Fluxametamide of Formula (I). The process of the present invention is a consistently reproducible process, which results in high yield, purity of Fluxametamide apart from resulting into stable form of Fluxametamide.

[0004] BACKGROUND OF THE INVENTION

[0005] Isoxazoline-substituted benzamide compound, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5- (trifluoromethyl)-3-isoxazolyl]-N-[(methoxyamino)methylene]-2-methylbenzamide also known as Fluxametamide having the structural Formula as represented by compound of Formula (I).

[0006] Fluxametamide Formula (I)

[0007] Fluxametamide is a novel wide- spectrum insecticide that was discovered and synthesized by Nissan Chemical Industries, Ltd. It is a potent inhibitor of y- aminobutyric acid (GABA)-, glutamate-, and glycine-gated chloride channels in insects. Fluxametamide is a wide-spectrum isoxazoline insecticide effective against a broad spectrum of pests. It is mainly used in the control of lepidopteran pests, thrips, whiteflies, leaf miners, beetles and mites on crops such as fruit trees, vegetables, soybeans, cotton and tea trees and other crops.

[0008] Synthesis of various isoxazoline-substituted benzamide compounds is known in the arts such as: U.S. Patent No. 7,662,972 which discloses the compound of Formula (I) and synthesis of various isoxazoline-substituted benzamide compounds. The prior art discloses the use of toxic and expensive reagents like carbon monoxide and need special equipments which are not easy to operate. Further, it also needs extensive pollution abetment systems for effectively eliminating toxic chemicals which also leads to higher pollution load. Accordingly, the process disclosed in the prior art involves the use of toxic and hazardous chemicals and requires specialized equipment, rendering it economically less viable and environmentally more detrimental in comparison to the process of the present invention.

[0009] International (PCT) Publication No. WO 2013 / 021949 discloses methods for producing substituted 4,4-difluoro-2-buten-l-one compounds and substituted isoxazoline compounds by carrying out a dehydration reaction in the presence of a phase transfer catalyst.

[0010] However, the processes described in the prior art are not suitable for efficient large-scale commercial production, primarily due to their reliance on toxic or hazardous reagents, stringent reaction conditions, and complex purification protocols. These limitations result in lower yields, suboptimal regioselectivity, poor reproducibility, and increased operational costs.

[0011] Therefore, there exists a need for an improved process that is more economical, environmentally benign, operationally simple, and industrially scalable for the synthesis of isoxazoline-substituted benzamide compounds, such as Fluxametamide of Formula (I).

[0012] Accordingly, the present invention addresses these deficiencies by providing a process for preparing Fluxametamide with enhanced overall yield, higher chemical and / or optical purity, and improved regio selectivity, while minimizing the use of hazardous materials and simplifying downstream processing — thereby making it suitable for commercial-scale manufacturing.

[0013] Accordingly, there exists a longstanding and unmet need for a robust, reproducible, and industrially scalable process for the preparation of Fluxametamide, which offers improved yield, enhanced chemical purity, and superior regio selectivity, while also being cost-effective and compliant with regulatory standards. H

[0014] Accordingly, it is an objective of the present invention to provide an improved process for the preparation of Fluxametamide under basic conditions, wherein the overall yield, purity, and regioselectivity are significantly enhanced. There remains a need for a simplified, cost- effective, environmentally benign, and consistently reproducible process capable of producing highly pure and stable Fluxametamide suitable for industrial-scale manufacturing. In view of the limitations associated with existing processes, the present invention provides an alternative and technically superior process that overcomes the drawbacks of the prior arts. The invention discloses a novel, inventive, and industrially viable process for the synthesis of Fluxametamide of Formula (I), which is amenable to scale-up and compliant with regulatory standards.

[0015] The present invention satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior arts.

[0016] OBJECTIVE AND ADVANTAGES OF INVENTION

[0017] The main objective of the present invention is to provide a simple, economically advantageous and cost-effective process for the preparation of Fluxametamide of Formula (I), with high purity and yield of Fluxametamide on a commercial scale.

[0018] Another objective of the present invention is to provide a novel and industrially feasible process for the preparation of Fluxametamide of Formula (I), either in its free form, in an agrochemically acceptable salt form, or in a formulated composition, starting from readily available, cost-effective, and operationally convenient intermediates that are stable and easy to handle.

[0019] Another objective of the present invention is to provide a novel and effective process for preparation of Fluxametamide of formula (I), with reduced or minimal waste generation.

[0020] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of Formula (I), with an improved reaction while substantially minimizing side reactions and / or the formation of undesirable by-products, thereby improving overall process efficiency and product purity.

[0021] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of formula (I), that involves less expensive and readily available reagents including but not limited to sodium nitrite, thionyl chloride, aluminum chloride, bases, acids and solvents including but not limited to ethylene dichloride (EDC), ethyl acetate (EA), acetone, acetic acid, acetonitrile. Another objective of the present invention is to provide a process for the preparation of Fluxametamide of formula (I), which is industrially and economically robust process with safe operations.

[0022] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of formula (I), which results in improved yield and purity of the final product.

[0023] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of formula (I), wherein, less effluent is generated.

[0024] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of Formula (I), along with its key intermediates and their respective synthetic routes, wherein the process is time-efficient and employs readily available, non-toxic, and non- hazardous reagents. The process avoids the use of hazardous chemicals and eliminates the need for specialized or high-maintenance equipment typically required in prior art processes.

[0025] Another objective of the present invention is to provide a process that affords a cleaner product with high yield and purity, while substantially minimizing or eliminating the formation of undesirable by-products.

[0026] Another objective of the present invention is to provide a process for the preparation of Fluxametamide of Formula (I), as well as its intermediates and their respective synthetic routes, wherein the reactions are carried out under milder conditions, such as moderate temperature and pressure, thereby enhancing operational safety and scalability.

[0027] Another objective of the present invention is to provide a process for the preparation of an intermediate compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4) by the sequential reactions starting from the compound of (Formula A-l), z.e., nitrobenzene.

[0028] Another objective of the present invention is to provide a process for the preparation of an intermediate compound, 4-(2-haloacetyl)-2-methylbenzamide of (Formula B-6), by the sequential reactions starting from the compound of (Formula B-l), z.e., acetophenone.

[0029] Another objective of the present invention is to provide a novel process for the preparation of Fluxametamide, either in its free form or as an agrochemically acceptable salt, which is suitable for subsequent formulation into appropriate agrochemical dosage forms.

[0030] Another objective of the present invention is to obtain a compound, 4-[(2E)-3-(3,5- dich lorophcny I )-4,4,4-tri fl uorobut-2-cnoy I] -2- methyl benzamide of (Formula 2), by reacting a compound l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4) with a compound, 4-(2-haloacetyl)-2-methylbenzamide of (Formula B-6) using Wittig or Wittig Homer reaction conditions.

[0031] Some or all these and other objects of the invention can be achieved by way of the invention described hereinafter.

[0032] Advantages of the present invention:

[0033] 1. The process, intermediates and process of preparation of intermediates of the present invention provides improved reaction time (utilizes less time), incorporates readily available reagents which are non-toxic and less / non-polluting without requiring any hazardous chemicals and special purpose equipments as used in the prior art documents.

[0034] 2. The process of the present invention provides better yield and high purity of the intermediates as well as the final product.

[0035] The process of the present invention affords a cleaner product with high chemical purity, while substantially minimizing or eliminating the formation of undesired by -products. The process for the preparation of Fluxametamide, as well as its intermediates and their respective synthetic routes, is conducted under milder reaction conditions, such as moderate temperature and pressure, thereby improving safety and operational efficiency.The present invention provides an industrially viable and economically robust process that enables safe, scalable, and cost- effective operations.

[0036] SUMMARY OF THE INVENTION

[0037] Accordingly, the main aspect of the present invention is to provide an alternative and improved process for the preparation of Fluxametamide of Formula (I). Provided herein is simple, cost effective and consistently reproducible process for the preparation of highly pure and stable form of Fluxametamide.

[0038] In an aspect, the present invention provides an alternative and improved process for the preparation of Fluxametamide of Formula (I), using cost effective and readily available reagents.

[0039] In another aspect, the present invention provides a process for the preparation of Fluxametamide of Formula (I), in simple manner and in good yield and purity. In another aspect, the present invention provides a process for the preparation of Fluxametamide of Formula (I), along with its intermediates and their respective synthetic routes, wherein the reactions are carried out under milder conditions, such as moderate temperature and pressure, thereby enhancing safety, energy efficiency, and scalability.

[0040] In an aspect, the present invention provides a process for the preparation of Fluxametamide of Formula (I), comprising: a) reacting a compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4) with a compound, 4-(2-haloacetyl)-2-methylbenzamide of (Formula B-6) using Wittig or Wittig Homer reaction conditions to obtain a compound, 4-[(2E)-3-(3,5- dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzamide of (Formula 2); b) reacting the compound of (Formula-2), with hydroxylamine hydrochloride in the presence of base followed by acid mediated ring cyclization to obtain a compound, 4- [5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzamide of (Formula 3); c) formylating the compound of (Formula 3), followed by reaction with methoxy amine hydrochloride (McONfE) / HC1 to obtain the target compound, z.e., Fluxametamide of Formula (I).

[0041] Another aspect of the present invention provides to obtain a compound, 4-[(2E)-3-(3,5- dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzamide of (Formula 2) by reacting a compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4) with a compound, 4-(2-haloacetyl)-2-methylbenzamide of (Formula B-6) using Wittig or Wittig Homer reaction conditions using reagents for instance, but not limited to triphenylphosphine (PPh3).

[0042] Another aspect of the present invention is to provide a process for the preparation of an intermediate compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4) by the sequential reactions starting from the compound of (Formula A-l), z.e., nitrobenzene.

[0043] Another objective of the present invention is to provide a process for the preparation of an intermediate compound, 4-(2-haloacetyl)-2-methylbenzamide of (Formula B-6), by the sequential reactions starting from the compound of (Formula B-l), z.e., acetophenone.

[0044] DETAILED DESCRIPTION OF THE INVENTION At the very outset of the detailed description, it may be understood that the ensuing description only illustrates a particular form of this invention. However, such a particular form is only exemplary embodiment, and without intending to imply any limitation on the scope of this invention. Accordingly, the description is to be understood as an exemplary embodiment and teaching of the invention and not intended to be taken restrictively.

[0045] The technical solutions of the present disclosure will be further described below by way of specific embodiments. It will be apparent to those skilled in the art that the embodiments are merely illustrations of the present disclosure and should not be construed as specific limitations to the present disclosure.

[0046] It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the present disclosure.

[0047] Certain ranges are presented herein with numerical values being preceded by the term “about”. The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximately unrecited number may be a number which in the context in which it is presented, provides the substantial equivalent of the specifically recited number. In an embodiment, “about” can mean within one or more standard deviations, or within ±30%, 25%, 20%, 15%, 10%, or 5% of the stated value.

[0048] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs. Although any process and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, preferred process is described. For the purposes of the present invention, the following terms are defined below:

[0049] The articles “a” and “an” are used herein to refer to one or to more than one (z.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0050] As used herein, the terms, “including”, “includes”, “comprising”, and comprises” mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items.

[0051] Each embodiment is provided by way of explanation of the invention and not by way of limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the process described herein without departing from the scope of the invention. For instance, features illustrated or described as part of one embodiment can be applied to another embodiment to yield a still further embodiment.

[0052] While various embodiments of the present invention have been described and illustrated herein, it will be apparent to those skilled in the art that numerous modifications, substitutions, and variations may be made without departing from the scope and spirit of the invention. Such equivalents and alternatives for achieving the described functions, results, or advantages are considered to be encompassed within the scope of the present invention.

[0053] Moreover, other than in any operating examples, or where otherwise indicated, all numbers expressing, for example, quantities of materials / ingredients used in the specification are to be understood as being modified in all instances by the term "about". The term "about" shall be interpreted to mean "approximately" or "reasonably close to" and any statistically insignificant variations therefrom.

[0054] Conventional methods for the preparation of Fluxametamide are associated with several limitations, including the use of toxic and hazardous reagents such as carbon monoxide, reliance on specialized equipment that is complex to operate, and a lack of clear disclosure regarding the attainment of high-purity end products. Moreover, these conventional processes often involve stringent reaction conditions and multistep operations, which collectively contribute to increased production costs and reduced process efficiency.

[0055] Accordingly, there exists a need for an improved, safer, and more cost-effective synthetic process that overcomes these disadvantages by utilizing readily available and less hazardous reagents, operating under milder and more manageable reaction conditions, and delivering Fluxametamide with enhanced yield, purity, and scalability. The present invention addresses these longstanding challenges and provides a technically superior and industrially viable alternative.

[0056] In an embodiment, the present invention provides a process for the preparation of Fluxametamide of Formula (I), comprising the following steps: i. Reacting l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4) with 4-(2- haloacetyl)-2-methylbenzamide (Formula B-6) under Wittig or Homer-Wadsworth-Emmons (HWE) reaction conditions to afford 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2- enoyl]-2-methylbenzamide (Formula 2); ii. Reacting the compound of Formula 2 with hydroxylamine hydrochloride in the presence of a base (e.g., NaOH, K2CO3), followed by acid-mediated cyclization, to yield 4-[5-(3,5- dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2-methylbenzamide (Formula 3); iii. Subjecting the compound of Formula 3 to formylation, followed by condensation with methoxyamine hydrochloride (MeONH2 HC1) under suitable coupling conditions to obtain the target compound, Fluxametamide of Formula (I).

[0057] In an embodiment, a compound of (Formula A-4), i.e., l-(3,5-dichlorophenyl)-2,2,2- trifluoroethan-l-one is obtained by the sequential reactions starting from Nitrobenzene of (Formula A-l), reacting nitrobenzene of Formula A-l in the presence of a halogenating reagents such as chlorine (CI2) or N-chlorosuccinimide (NCS), to provide a compound, 1,3- dichloro-5-nitrobenzene of (Formula A-2). This intermediate Formula A-2 compound is then reduced and thus converted to an intermediate compound such as 3, 5 -Dichloroaniline, which is then converted to a compound, l-bromo-3,5-dichlorobenzene of (Formula A-3) by reduction in the presence of suitable catalysts including but not limited to Pd / C, in presence of hydrogen gas and diazotization using the reagents like sodium nitrite (NaNCF) and cuprous bromide (CuBr) to get the corresponding aryl bromide, such reaction conditions are known to the person skilled in the art. The reaction conditions for halogenation, reduction, diazotization, are well known in the art and can be suitably optimized by a person skilled in the field of synthetic organic chemistry.

[0058] In one of the embodiments, the compound of (Formula A-3) namely l-bromo-3,5- dichlorobenzene is subjected to Grignard reaction to form the corresponding aryl magnesium intermediate. The reaction is carried out using activated magnesium turnings and crystals of iodine in the presence of trifluoroacetaldehyde gas followed by oxidation in the presence of an oxidizing agents for instance, but not limited to manganese dioxide (MnCF) or PCC (pyridinium chlorochromate) in dichloromethane or acetone, to obtain target ketone, a compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4), i.e., l-(3,5- dichlorophenyl)-2,2,2-trifluoroethan-l-one. The reaction conditions for Grignard formation, and oxidation are well established in the art and may be optimized by a person skilled in synthetic organic chemistry.

[0059] In another embodiment, the present invention provides that the compound of (Formula B-6), i.e., 4-(2-haloacetyl)-2-methylbenzamide is obtained by the methylation of acetophenone of (Formula B-l) in the presence of methylating agents and Lewis acid to obtain a compound, 3- Methylacetophenone of (Formula B-2).

[0060] In one of the embodiments, mono -halogenation of aromatic ring of the compound of (Formula B-2), namely 3 -Methylacetophenone is carried out in the presence of a suitable catalysts selected from the group comprising 5-10% Pd on Charcoal or 5% Pt on Charcoal, ZSM-5, Cu(I) salts, trichloroisocyanuric acid (TCICA), Trifluoroacetic acid, Fe (III) salts, Aluminum chloride (A1C13), Ferric bromide (FeBn), Ferric chloride (FeCL), A,A-Di methyl formamide (DMF), Azobisisobutyronitrile (AIBN), trichloroisocyanuric acid (TCICA), or combination thereof, halogenating agents selected from the group comprising X2, HX, wherein X = Br, Cl, I, A- Bro mo succinimide (NBS), chlorine gas, A-chlorosuccinimide (NCS), Thionyl chloride, phosphorus pentachloride, phosphorus tribromide, hydrogen bromide, hydrogen peroxide, sulfuryl chloride, phosphorus trichloride, to obtain a compound, l-(4-halo-3- methylphenyl)ethan- l-one of (Formula B-3) which is further reacted with n-butyl lithium under controlled low-temperature conditions to generate the corresponding aryllithium intermediate, which is subsequently quenched with carbon dioxide (CO2) to provide the carboxylated product i.e., 4-acetyl-2-methylbenzoic acid of (Formula B-4).

[0061] In one of the embodiments, the 4-acetyl-2-methylbenzoic acid (Formula B-4) is converted to the corresponding acid chloride using a chlorinating reagent in the presence of the reagents and suitable catalysts. The resulting acid chloride is subsequently subjected amidation in the presence of aqueous ammonia to provide a compound, 4-acetyl-2-methylbenzamide (Formula B-5). This intermediate is then further transformed into compound 4-(2-haloacetyl)-2-methylbenzamide (Formula B-6) by halogenation via a-halogenation of the acetyl group using reagents, using the procedure known to the skilled in the art. The halogenation conditions and reagents employed are well known in the art and may be selected and optimized by a person skilled in synthetic organic chemistry. In another embodiment, the present invention provides a process for the preparation of Fluxametamide of Formula (I), wherein the process comprises the step of reacting l-(3,5- dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4) with 4-(2-haloacetyl)-2- methylbenzamide (Formula B-6), wherein the halogen (X) is selected from Cl, Br, or I, under Wittig or Horner-Wadsworth-Emmons (Wittig-Homer) reaction conditions.

[0062] The reaction is carried out using a phosphonium salt or phosphonate ester, in the presence of a base, and optionally in the presence of a solvent. Suitable reagents include, but are not limited to, triphenylphosphine (PPhs) in combination with a base such as n-butyllithium, sodium hydride (NaH), or potassium tert-butoxide, to afford the corresponding a,P-unsaturated amide, 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzamide (Formula 2), as depicted in [Scheme- 1].

[0063] [Scheme-1]

[0064] In an embodiment, the compound of (Formula A-4), namely., l-(3,5-dichlorophenyl)-2,2,2- trifluoroethan-l-one is obtained by sequential reactions starting from nitrobenzene (Formula A-l) as illustrated in [Scheme-2].. Initially, n, nitrobenzene of (Formula A-l) is subjected to electrophilic halogenation using one or more chlorinating reagents selected from the group comprising chlorine gas, sulfuryl chloride, phosphorus trichloride, phosphorous pentachloride, N-chlorosuccinimide (NCS) in the presence of a suitable halogenation catalyst, to obtain a compound, l,3-dichloro-5-nitrobenzene (Formula A-2). Suitable catalysts for the halogenation include, but are not limited to, Cu(I) salts, trichloroisocyanuric acid (TCICA), Trifluoroacetic acid, Fe(III) salts, Aluminum chloride (A1C13), Ferric bromide (FeBr3), , Ferric chloride (FeCh) ferric bromide (FeB ), aluminum chloride (AICL). and other Fe(III) salts, which facilitate regioselective chlorination to afford Compound of (Formula A-2). The The compound of Formula A-2 is then subjected to reduction and hence converted to an intermediate compound such as 3,5- Dichloroaniline, which is then converted to the compound (Formula A-3), l-bromo-3,5- dichlorobenzene by reduction and diazotization using reagents like sodium nitrite and Cuprous bromide (CuBr) to get the corresponding aryl bromide followed by Sandmeyer reaction using the reaction conditions known to the skilled in the art. The individual steps and conditions for halogenation, reduction, diazotization, and aryl bromide formation are well established in the art and may be optimized or varied by a person skilled in the field of synthetic organic chemistry.

[0065] The compound (Formula A-3), i.e., l-bromo-3,5-dichlorobenzene is subjected to Grignard reaction involving activated magnesium turnings and a catalytic amount of iodine crystals, under anhydrous conditions to generate the corresponding aryl magnesium bromide intermediate. This intermediate is then reacted with trifluoroacetaldehyde gas to yield the corresponding secondary alcohol. The resulting alcohol is subsequently oxidized to the corresponding ketone using an oxidizing agent selected from the group comprising manganese dioxide (MnCL), pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), or Jones reagent, thereby affording the desired product, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l- one (Formula A-4).

[0066] [Scheme-2]

[0067] Further, the compound of Formula B-2, namely 3 -methylacetophenone, is obtained by the methylation of acetophenone (Formula B-l), as illustrated in [Scheme-3]. The methylation is carried out using a methylating agent selected from the group comprising methyl iodide (CFbl), methyl bromide (CFbBr), or methyl chloride (CFbCl), in the presence of a Lewis acid catalyst selected from the group comprising aluminum chloride (A1CL), titanium tetrachloride (TiCL), ferric chloride (FeCL), or zinc chloride (ZnCL). The reaction selectively introduces a methyl group at the meta-position of the aromatic ring, affording 3 -methylacetophenone (Formula B- 2). The methylation reaction conditions, including temperature, solvent, and reagent ratios, may be varied and optimized by a person skilled in the art to achieve the desired yield and regioselectivity.

[0068] Mono-halogenation of the aromatic ring of the compound of Formula B-2, namely 3- methylacetophenone, is carried out using a halogenating agent selected from the group comprising molecular halogens (X2) or hydrogen halides (HX), wherein X = Cl, Br, I, or F, to yield the halogenated intermediate. This intermediate is then treated with n-butyllithium (n- BuLi) under low-temperature conditions to generate the corresponding aryllithium species, which is subsequently reacted with carbon dioxide (CO2) to afford 4-acetyl-2-methylbenzoic acid (Formula B-4).

[0069] The compound of Formula B-4 is then converted to the corresponding acid chloride using a chlorinating reagent selected from the group comprising thionyl chloride (SOCh), sulfuryl chloride (SO2CI2), or phosphorus oxychloride (POCh), optionally in the presence of a suitable catalyst. The resulting acid chloride is subsequently amidated using ammonia (NH3) to afford 4-acetyl-2-methylbenzamide (Formula B-5).

[0070] Finally, the compound of Formula B-5 is converted to 4-(2-chloroacetyl)-2-methylbenzamide (Formula B-6) through a-halogenation of the acetyl group using a halogenating reagent under standard conditions known to those skilled in the art.

[0071] [Scheme-3]

[0072] The compound of Formula (2), namely 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2- enoyl]-2-methylbenzamide, is reacted with hydroxylamine hydrochloride in the presence of a base selected from, but not limited to, sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium methoxide (NaOMe), triethylamine (EtsN), pyridine, diisopropylamine, potassium carbonate (K2CO3), or sodium carbonate (Na2COs). This reaction forms the corresponding oxime intermediate, which is then subjected to acid-mediated cyclization to yield the compound of Formula (3), identified as 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5- dihydro- 1 ,2-oxazol-3 -yl] -2-methylbenzamide. The base-mediated oximation and subsequent cyclization are carried out under conditions known in the art, and may be optimized for temperature, solvent, and reagent concentrations to improve yield, regio selectivity, and purity. In the final step, the compound of Formula (3) is reacted with methoxyamine hydrochloride (MeONFE HCl) in the presence of a coupling agent such as N,N'-dicyclohexylcarbodiimide (DCC) or N,N'-diisopropylcarbodiimide (DIC), optionally in the presence of a base like triethylamine (EfeN) or a catalyst such as 4- dimethylaminopyridine (DMAP), to afford the target compound Fluxametamide of Formula (I), as illustrated in [Scheme-4].

[0073] The reaction is typically carried out in an inert solvent such as dichloromethane (DCM), dimethylformamide (DMF), or tetrahydrofuran (THF), under conditions known to those skilled in the art and optimized for high yield and purity.

[0074] [Scheme-4]

[0075] In one of the embodiments, the compound 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut- 2-enoyl]-2-methylbenzamide (Formula 2) is synthesized by the Wittig or Homer-Wadsworth- Emmons (HWE) reaction of l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4) with 2-methyl-4-propanoylbenzamide (Formula B-6), under appropriate base and solvent conditions known in the art.

[0076] In a related embodiment, the compound l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4) is prepared by subjecting l-bromo-3,5-dichlorobenzene (Formula A-3) to a Grignard reaction using activated magnesium turnings and catalytic amounts of iodine crystals, followed by reaction with trifluoroacetaldehyde gas. The resulting alcohol intermediate is then oxidized using a suitable oxidizing agent, such as manganese dioxide (MnCF), pyridinium chlorochromate (PCC), or Dess-Martin periodinane, to afford the ketone of Formula A-4. In one of the embodiments, the compound 4-acetyl-2-methylbenzoic acid (Formula B-4) is prepared by treating l-(4-halo-3-methylphenyl)ethan-l-one (Formula B-3) with n-butyllithium (n-BuLi) under inert and low-temperature conditions to generate the corresponding aryllithium intermediate, which is subsequently quenched with carbon dioxide (CO2) to afford the desired carboxylic acid derivative, i.e., compound of Formula B-4.

[0077] In one of the embodiments, the base is selected from the group comprising diisopropylamine, N,N-diisopropylethylamine (DIPEA), triethylamine (EtsN), dimethylamine, trimethylamine, pyridine, N-methylmorpholine (NMM), 2-picoline, 3-picoline, 4-picoline, sodium hydroxide (NaOH), potassium hydroxide (KOH), n-butyllithium (n-BuLi), sodium carbonate (Na2COs), sodium bicarbonate (NaHCCF), sodium acetate (CHsCOONa), potassium carbonate (K2CO3), calcium hydroxide (Ca(OH)2), sodium methoxide (NaOMe), or a combination thereof.

[0078] In one of the embodiments, the suitable solvent is selected from the group comprising ethylene chloride, ethylene dichloride (EDC), methylene dichloride (MDC), chlorobenzene, o- dichlorobenzene, dichlorobenzene, chloroform, carbon tetrachloride, benzene, toluene, xylene, 1,4-dioxane, diethyl ether, tetrahydro furan (THF), acetonitrile, ethyl acetate, acetone, methanol, isopropanol (IPA), 2-propanol, cyclohexane, hexane, heptane, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetic acid, hydrogen peroxide, phosphorus oxychloride (POCE), water, brine, sodium sulfate, or a combination thereof, depending on the nature of the reaction and solubility requirements.

[0079] In one of the embodiments, the process of acid-mediated cyclization is carried by using acids such as organic or inorganic acid, mineral acids.

[0080] In one of the embodiments, the acid is selected from the group comprising acetic acid, formic acid, citric acid, lactic acid, oxalic acid, benzoic acid, salicylic acid, pyruvic acid, sulfanilic acid, p-toluenesulfonic acid (p-TsOH), 3 -chlorobenzoic acid, ketone-derived carboxylic acids, hydrochloric acid (HC1), sulfuric acid (H2SO4), nitric acid (HNO3), phosphoric acid (H3PO4), hydrofluoric acid (HF), or a combination thereof, depending on the desired reaction environment

[0081] In one of the embodiments, the acid is selected from either organic acids or inorganic acids, depending on the nature of the reaction.

[0082] • Organic acids include, but are not limited to: — Acetic acid

[0083] — Formic acid

[0084] — Citric acid

[0085] — Lactic acid

[0086] — Oxalic acid

[0087] — Benzoic acid

[0088] — Salicylic acid

[0089] — Pyruvic acid

[0090] — Sulfanilic acid

[0091] — p-Toluenesulfonic acid (p-TsOH)

[0092] — 3 -Chlorobenzoic acid

[0093] — Other ketone-derived carboxylic acids

[0094] • Inorganic acids include, but are not limited to:

[0095] — Hydrochloric acid (HC1)

[0096] — Sulfuric acid (H2SO4)

[0097] — Nitric acid (HNO3)

[0098] — Phosphoric acid (H3PO4)

[0099] — Hydrofluoric acid (HF)

[0100] In one of the embodiments, the formylating agent is selected from the group comprising paraformaldehyde, formalin (aqueous formaldehyde solution), formic acid, methyl formate, N,N-dimethylformamide (DMF), phosphorus oxychloride (POCL), diazomethane, cyanogen bromide, hydrogen cyanide (HCN), or a combination thereof, depending on the desired mode of formylation and reaction compatibility. In one of the embodiments, the amidation is carried out using reagents selected from the group comprising ammonia gas (NH3), aqueous ammonia, ammonium acetate, ammonium formate, or a combination thereof, depending on the nature of the substrate and desired reaction conditions.

[0101] In one of the embodiments, the halogenating agent is selected from the group comprising chlorine gas (CL), bromine (B ), iodine (L), N-chlorosuccinimide (NCS), N- bromosuccinimide (NBS), thionyl chloride (SOCI2), sulfuryl chloride (SO2CI2), phosphorus trichloride (PCL), phosphorus pentachloride (PCL), phosphorus tribromide (PBn), hydrogen halides (HX) wherein X = Cl, Br, I, hydrogen bromide (HBr), hydrogen peroxide (H2O2), and combinations thereof. The halogenation may optionally be carried out in the presence of acetic acid, sulfuric acid (H2SO4), potassium salts, or oxidants such as hydrogen peroxide, depending on the nature of the substrate and the desired degree of halogenation.

[0102] In a preferred embodiment, the halogenating agent is a chlorinating agent.In one of the embodiments, the catalyst is selected from the group comprising 5-10% palladium on charcoal (Pd / C), 5% platinum on charcoal (Pt / C), ZSM-5 zeolite, copper(I) salts (e.g., CuBr, CuCl), trichloroisocyanuric acid (TCICA), trifluoroacetic acid (TFA), iron(III) salts such as ferric chloride (FeCk) or ferric bromide (FeBrs), aluminum chloride (AICk), N,N- dimethylformamide (DMF) when used as a polar aprotic catalyst medium, azobisisobutyronitrile (AIBN) as a free radical initiator, or a combination thereof, In one of the embodiments, the methylating agent is selected from the group comprising methyl iodide (Mel), dimethyl sulfate (DMS), methyl chloride (MeCl), methyl bromide (MeBr), dimethyl carbonate (DMC), diazomethane, dimethylamine, or a combination thereof, depending on the substrate and reaction conditions.

[0103] In another embodiment, the Lewis acid is selected from the group comprising zinc chloride (ZnCk), aluminum chloride (AICL), ferric chloride (FeCk), boron trifluoride (BF3), boron trichloride (BCk), titanium tetrachloride (TiCk), antimony pentafluoride (SbFs), copper(II) chloride (CuCk), metal triflates (such as scandium triflate or yttrium triflate), zeolites, or a combination thereof, depending on the desired catalytic activity and selectivity. In one of the embodiments, the oxidizing agent is selected from the group comprising manganese dioxide (MnCh), pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), Jones reagent (chromic acid in acetone), or a combination thereof, depending on the desired level of oxidation.

[0104] The process for the preparation of Fluxametamide of Formula (I), as disclosed in the present invention, results in the formation of Fluxametamide with a purity ranging from about 95% to 99% and a yield exceeding about 80%.

[0105] It should be understood that the description of the present invention has been intentionally simplified and focused to emphasize elements that are most relevant for a clear and concise understanding of the invention. Certain elements or details that may be well known to those skilled in the art have been omitted for the sake of brevity and clarity. To further facilitate understanding of the invention as disclosed and claimed herein, the following definitions and abbreviations are provided: Formula A-l: Nitrobenzene, Formula A-2: l,3-dichloro-5-nitrobenzene,

[0106] Formula A-3: l-bromo-3,5-dichlorobenzene,

[0107] Formula A-4: l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one,

[0108] Formula B-l: 1-phenylethan-l-one, or acetophenone

[0109] Formula B-2: l-(3-methylphenyl)ethan-l-one, or 3 -Methylacetophenone

[0110] Formula B-3: 4'-Bromo-3'-methylacetophenone,

[0111] Formula B-4: 4-acetyl-2-methylbenzoic acid,

[0112] Formula B-5: 4-acetyl-2-methylbenzamide,

[0113] Formula B-6: 4-(2-haloacetyl)-2-methylbenzamide.

[0114] Formula (2): 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzamide, Formula (3): 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzamide,

[0115] Formula (I)- Fluxametamide

[0116] In one of the embodiments, the present invention provides a process for the preparation of Fluxametamide of Formula (I), comprising the steps of: i. Reacting a compound, l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4), with 4-(2-bromoacetyl)-2-methylbenzamide (Formula B-6) in the presence of sodium methoxide (NaOMe) and a suitable solvent, to obtain 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-2-enoyl]-2-methylbenzamide (Formula 2); ii. Reacting the compound of Formula 2 obtained in step (i) with hydroxylamine hydrochloride in the presence of a base and suitable solvent, followed by acid-mediated cyclization, to obtain 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3- yl]-2-methylbenzamide (Formula 3); iii. Formylating the compound of Formula 3 obtained in step (ii), followed by reaction with methoxyamine hydrochloride (MeONFE HC1), to afford the final product, Fluxametamide of Formula (I).

[0117] In one of the embodiments, the present invention provides a process for the preparation of the compound l-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4), wherein the compound of Formula A-4 is synthesized via the following sequential steps: i) Reacting nitrobenzene of Formula A-l with one or more halogenating agents in the presence of suitable solvents and optionally catalysts, to afford l,3-dichloro-5-nitrobenzene (Formula A-2); ii) Reducing the compound of Formula A-2, followed by diazotization and substitution using brominating agents to yield l-bromo-3,5-dichlorobenzene (Formula A-3); iii) Subjecting the compound of Formula A-3 to a Grignard reaction using activated magnesium and trifluoroacetaldehyde, followed by oxidation in the presence of one or more oxidizing agents and suitable solvents, to obtain the desired compound, l-(3,5- dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4).

[0118] In one of the embodiments, the present invention provides a process for the preparation of 1- (3,5-dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4), comprising the following steps:

[0119] Nitrobenzene (Formula A-l) is reacted with chlorine gas or N-chlorosuccinimide (NCS) in the presence of a Lewis acid catalyst such as aluminum chloride (AICL) or ferric chloride (FeCL) and a solvent such as dichloromethane (DCM) or carbon tetrachloride (CCh). The reaction is maintained at a temperature between 0°C to 25°C under stirring to afford l,3-dichloro-5- nitrobenzene (Formula A-2). The progress of the reaction is monitored by TLC or GC-MS.

[0120] The compound of Formula A-2 is subjected to reduction using a reducing agent such as iron powder in acidic medium (e.g., HC1) or SnCL in ethanol, to give 3,5-dichloroaniline. The resulting amine is then diazotized using sodium nitrite (NaNO?) in aqueous HC1 at 0-5°C, followed by treatment with cuprous bromide (CuBr) to afford l-bromo-3,5-dichlorobenzene (Formula A-3) via a Sandmeyer reaction.

[0121] The compound of Formula A-3 is reacted with activated magnesium turnings in anhydrous diethyl ether or THF under a nitrogen atmosphere, with a catalytic amount of iodine crystals to initiate Grignard formation. Once the Grignard reagent is formed, trifluoroacetaldehyde gas is bubbled into the reaction mixture at 0°C to room temperature. After complete conversion, the reaction mixture is subjected to oxidation using an oxidizing agent such as manganese dioxide (MnCF) or PCC (pyridinium chlorochromate) in dichloromethane or acetone, to afford l-(3,5- dichlorophenyl)-2,2,2-trifluoroethan-l-one (Formula A-4).

[0122] The product is then isolated by extraction, washed with brine, dried over anhydrous sodium sulfate, and purified by recrystallization or chromatography to yield the target compound with a purity typically exceeding 95%, as confirmed by HPLC or NMR spectroscopy.

[0123] In one of the embodiments, the present invention provides a process for the preparation of the compound 4-(2-haloacetyl)-2-methylbenzamide of Formula B-6, wherein the compound is obtained through the following sequential steps: i. Methylation of acetophenone (Formula B-l) using a suitable methylating agent, in the presence of a Lewis acid and appropriate solvents, to obtain 3 -methylacetophenone (Formula B-2); ii. Mono-halogenation of the aromatic ring of the compound of Formula B-2, obtained in step (i), in the presence of one or more halogenating agents and a suitable catalyst, to afford 4'- bromo-3'-methylacetophenone (Formula B-3); iii. Reaction of the compound of Formula B-3, obtained in step (ii), with a suitable base, followed by carboxylation using carbon dioxide, to obtain 4-acetyl-2-methylbenzoic acid (Formula B-4); iv. Conversion of the compound of Formula B-4, obtained in step (iii), to the corresponding acid chloride using appropriate reagents and solvents, followed by amidation with a suitable nitrogen source, to yield 4-acetyl-2-methylbenzamide (Formula B-5); v. Halogenation of the compound of Formula B-5, obtained in step (iv), using suitable halogenating agents, to produce the target compound 4-(2-haloacetyl)-2-methylbenzamide of Formula B-6. In one of the embodiments, the present invention provides a process for the preparation of the compound 4-(2-haloacetyl)-2-methylbenzamide of Formula B-6, wherein the compound is synthesized via the following sequential steps: i. Methylation of acetophenone (Formula B-l) using a methylating agent selected from the group comprising methyl iodide, methyl bromide, or dimethyl sulfate, in the presence of a Lewis acid such as aluminum chloride (A1CL) or zinc chloride (ZnCL), and a suitable solvent such as dichloromethane or carbon disulfide, to afford 3 -methylacetophenone (Formula B-2); ii. Mono-halogenation of the aromatic ring of the compound of Formula B-2 obtained in step (i) using a halogenating agent selected from bromine (B ) or N-bromosuccinimide (NBS) in the presence of a catalyst such as iron(III) bromide (FcBn) or A1CL, to obtain 4'-bromo-3'- methylacetophenone (Formula B-3); iii. Metalation of the compound of Formula B-3 using n-butyllithium at low temperature (typically -78°C), followed by treatment with carbon dioxide (CO2) to yield 4-acetyl-2- methylbenzoic acid (Formula B-4); iv. Conversion of the acid of Formula B-4 into the corresponding acid chloride using reagents such as thionyl chloride (SOCI2) or oxalyl chloride in the presence of a solvent like chloroform or dichloromethane, followed by amidation with aqueous ammonia, ammonia gas, or ammonium salts, to obtain 4-acetyl-2-methylbenzamide (Formula B-5); v. Halogenation of the compound of Formula B-5 using a halogenating agent selected from bromine, N-bromosuccinimide (NBS), or thionyl chloride, to obtain the target compound, 4- (2-haloacetyl)-2-methylbenzamide of Formula B-6, wherein the halo group is preferably bromo or chloro.

[0124] In one of the embodiments, the formylation of the compound of Formula 3 is carried out in the presence of a formylating agent selected from, but not limited to, formic acid, paraformaldehyde, formalin, methyl formate, or N,N-dimethylformamide (DMF) in combination with suitable activating reagents and / or catalysts.

[0125] In another embodiment, the acid-mediated cyclization of the intermediate compound is performed in the presence of an acid, which may be selected from the group consisting of inorganic acids, mineral acids, and organic acids, including but not limited to hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, formic acid, p-toluenesulfonic acid (PTSA), or combinations thereof, depending on the desired selectivity.

[0126] In one of the embodiments, the oxidizing agent is selected from the group comprising, but not limited to, manganese dioxide (MnCL), pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), Jones reagent, chromium trioxide (CrCh), potassium permanganate (KMnCb), Dess-Martin periodinane, or a combination thereof, depending on the substrate and reaction conditions employed.

[0127] In one of the embodiments, the corresponding acid chloride is prepared using reagents selected from the group comprising, but not limited to, thionyl chloride, sulfuryl chloride, phosphorus oxychloride, or combinations thereof, optionally in the presence of a catalytic amount of N,N- dimethylformamide (DMF) or other activating agents, under suitable reaction conditions.

[0128] In another embodiment, the catalyst employed in the process is selected from the group comprising, but not limited to, 5-10% palladium on charcoal (Pd / C), 5% platinum on charcoal (Pt / C), zeolites such as ZSM-5, copper(I) salts, trichloroisocyanuric acid (TCICA), trifluoroacetic acid (TFA), ferric salts including Fe(III) chloride (FeCh), ferric bromide (FeBrs), aluminum chloride (AlCh), N,N-dimethylformamide (DMF) (when used as a catalyst or promoter), and azobisisobutyronitrile (AIBN), or any suitable combination thereof, depending on the specific transformation involved.

[0129] In one of the embodiments, the methylating agent is selected from the group comprising methyl iodide, dimethyl sulfate, methyl chloride, methyl bromide, dimethylcarbonate, diazomethane, dimethyl amine, or combination thereof.

[0130] In one of the embodiments, the Lewis acid is selected from the group comprising Zinc chloride (ZnCh), Aluminium Chloride (A1CL), Ferric Chloride (FeCL), Boron Trifluoride (BF3), Boron Trichloride (BCI3), Titanium tetrachloride (TiCL), Antimony Pentafluoride (SbFs), Copper Chloride (CuCh), any metal triflates or Zeolites or combination thereof. In one of the embodiments, the base is selected from the group comprising di-isopropylamine, diisopropylethylamine, tri-ethylamine, dimethylamine, trimethyl amine, pyridine, N- methylmorpholine, 3-picoline, 2-picoline, 4-picoline, sodium hydroxide, potassium hydroxide, n-butyl lithium, sodium carbonate, sodium bicarbonate, sodium acetate, potassium carbonate, or their bicarbonate salts, calcium hydroxide, sodium methoxide (NaOMe) or combination thereof.

[0131] In one of the embodiments, the halogenation reaction is carried out in the presence of a suitable halogenating agent, under controlled conditions appropriate to the substrate and desired selectivity.

[0132] In one of the embodiments, the halogenating agent is selected from the group comprising, but not limited to, chlorine gas, bromine, iodine, N-chlorosuccinimide (NCS), N- bromosuccinimide (NBS), thionyl chloride (SOCh), sulfuryl chloride (SO2CI2), phosphorus trichloride (PCk), phosphorus pentachloride (PCls), phosphorus tribromide (PB ), hydrogen halides (e.g., HC1, HBr, HI), hydrogen peroxide (H2O2), optionally in combination with acetic acid, potassium halide salts, sulfuric acid (H2SO4), or other acidic or catalytic media, or any combination thereof. .

[0133] In one of the embodiments, the amidation reaction is carried out using suitable reagents selected from the group comprising, but not limited to, ammonia gas, aqueous ammonia, ammonium acetate, ammonium formate, ammonium hydroxide, or a combination thereofln one of the embodiments, the formylating agent is selected from the group comprising, but not limited to, paraformaldehyde, formalin, formic acid, methyl formate, N,N- dimethylformamide (DMF), phosphorus oxychloride (POCI3), diazomethane, cyanogen bromide, hydrogen cyanide, or a combination thereof, optionally in the presence of a base, catalyst, or activating agent.

[0134] In one of the embodiments, the suitable solvents are selected from the group comprising ethylene chloride, ethylene dichloride (EDC), methylene dichloride (MDC), chlorobenzene, methanol, ethyl acetate, acetic acid, imcthy I formamide (DMF), benzene, chloroform, 1, 4-dioxane, diethyl ether, acetic acid, hydrogen peroxide, o-dichlorobenzene, carbon tetrachloride, chlorobenzene, dichlorobenzene, tetrahydrofuran (THF) and acetonitrile, ethyl acetate, acetone, dimethylsulfoxide, cyclohexane, hexane, heptane, toluene, xylene, Isopropanol (IPA), 2-propanol, Phosphorous oxychloride, water, brine, sodium sulfate or combination thereof.

[0135] In one of the embodiments, the Fluxametamide of Formula (I) may be obtained and isolated as its free form, as an agrochemically acceptable salt, or as a formulated composition, or other agrochemical dosage forms suitable for application.

[0136] In one of the embodiments, an agrochemical composition comprising Fluxametamide of Formula (I) as obtained by the process of the present invention.

[0137] In one of the embodiments, an agrochemical composition, wherein the composition comprises at least a bio-active effective amount of Fluxametamide of Formula (I) as obtained by the process of the present invention.

[0138] In one of the embodiments, the agrochemical composition further comprises one of more agrochemically acceptable excipients.

[0139] In one of the embodiments, a process for preparing the agrochemical composition comprising Fluxametamide of Formula (I) of the present invention.

[0140] The process of the present invention for the preparation of compound of Formula I, is represented stepwise in scheme provided below:

[0141]

[0142] Fluxamitamide (Formula I)

[0143] According to one of the embodiments, the preparation of compound l,3-Dichloro-5- nitrobenzene (A-2) comprises of three methods such as Method A; or Method B; or Method C.

[0144] In another embodiment, method A for the process of preparation of l,3-Dichloro-5- nitrobenzene (A-2) comprises reactor fitted with different apparatus for instance but not limited to condenser, pockets comprising thermometer, thermometer, stirrer, tube. The tube is connected to the setup for halogen gas quenching. Charging of nitrobenzene (A-l), using catalysts for instance but not limited to A1C13 for chlorination into the reactor. Heating and maintaining the reaction mass at a higher temperature above 800C. Passing of halogenating agent such a way that there is no escaping of halogenating agent for about 5-9 hrs. Maintaining the reaction at above 800C, preferably above 90° C for about more than 15 hrs. Cooling of reaction to room temperature rt. Diluting the reaction mass with Ethylene dichloride (EDC) and pouring over base solution and stirring for 10 mins - 1 hr. Separating the formed organic layer. Washing of the aqueous layer with EDC. Washing of combined organic layer with brine, dried over anhydrous sodium sulphate, filtering and concentrating to furnish l,3-Dichloro-5- nitrobenzene (A-2). After purification, purity is found to be above 94%, Yield: is found to be atleast above 60%.

[0145] In another embodiment, method B for the process of preparation of l,3-Dichloro-5- nitrobenzene (A-2) comprises reactor fitted with different auxiliary apparatus including but not limited to condenser, thermometer pocket, thermometer, stirrer, tubes. The tube is connected to the setup for halogen gas quenching. Charging of reactor with acid which is followed by Formula A- 1 (Nitrobenzene), lewis acid or halogenating agent and temperature is maintained above 100° C. Passing of halogenating agent such that halogenating agent escapes for about 1- 4 hrs. Maintaining the reaction maintained at above 100° C for above 15hrs followed by cooling to room temperature (rt). Diluting the reaction mass with solvent (for instance EDC)and pouring carefully over aqueous base solution. The pH is adjusted to around 7-9 and stirred for about 10 mins-1 hr. Separating the organic layer. Washing the aqueous layer with EDC. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulphate, and filtered and concentrated to furnish 1, 3 -Dichloro-5 -nitrobenzene (A-2). After purification, purity is found to be above 91%, Yield is found to be above 66%.

[0146] In another embodiment, method C for the process of preparation of l,3-Dichloro-5- nitrobenzene (A-2) comprises reactor fitted with different auxiliary apparatus including but not limited to condenser, pockets comprising thermometer, thermometer, stirrer, tube. Charging of reactor with EDC followed by Formula A-l (Nitrobenzene) with lewis acid, halogenating agent. Heating the reaction mass above 700C and maintained. Halogenating agent, preferably chlorinating agent is added portion wise. Maintaining the reaction above 70° C for about 20- 30 hrs. After completion of the reaction, the formed compound is filtered. The residue is washed with EDC. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulfate, and filtered and concentrated under vacuum to furnish 1,3-Dichloro- 5 -nitrobenzene (A-2). After purification, the purity and yield are calculated. The purity is found to be above 93%, and yield is found to be above 64%.

[0147] In another embodiment, wherein the process of preparation of l-Bromo-3,5-dichlorobenzene (A-3) comprises a reactor, and l,3-Dichloro-5-nitrobenzene (A-2) is charged and followed by suitable solvent. Catalyst is charged carefully to this mixture. The reactor is closed and then flushed with nitrogen gas multiple times. Nitrogen gas is removed and replaced with Hydrogen gas which is applied at a certain pressure. Stirring is done and continued the applied pressure of hydrogen gas is maintained by refilling to make up the pressure. The reaction is monitored by techniques such as TLC and HPLC. After completion of the reaction, hydrogen gas is vented out carefully in another container. The reaction mass is filtered and washed with suitable solvent. Formed combined layer is concentrated under vacuum to furnish intermediate compound (3,5-Dichloroaniline). This intermediate is then used for the next step.

[0148] In a reactor fitted with different apparatus including but not limited to condenser, thermometer pocket, thermometer, stirrer, crude material (3,5-Dichloroaniline) is dissolved in aqueous halogenating agent solution and cooled.

[0149] Sodium nitrite is dissolved in water was added without allowing the reaction mass temperature to rise above a certain temperature. After completion of the addition, the reaction is maintained at the same temperature for about 10 mins -1 hr. Cuprous bromide is added in lots at the same temperature. After such addition, the reaction is allowed to warm and is monitored by techniques like TLC and HPLC. The evolution of Nitrogen gas is observed. After completion, ethylene chloride is added and the organic layer was separated. The aqueous layer is washed with solvents like EDC. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulphate, and is filtered and concentrated to furnish l-Bromo-3,5- dichlorobenzene (A-3). After purification, purity and yield are calculated and purity is found to be above 94%, yield is above 70%.

[0150] In another embodiment, the process of preparation of l-(3,5-Dichlorophenyl)-2,2,2- trifluoroethan-l-one (A-4) comprises a flask fitted with different apparatus including but not limited to double surface condenser, thermometer pocket, thermometer, stirrer which is maintained under nitrogen atmosphere and is charged with solvents like Tetrahydrofuran (THF) , freshly activated magnesium turnings and few crystals of iodine. A small aliquot of 1- Bromo-3,5-dichlorobenzene (A-3) and solvent like dry THF is added. The reaction mass is warmed to initiate the reaction. Once the formation of Grignard reagent set in, the remaining of l-Bromo-3,5-dichlorobenzene (A-3) is suitably added at a rate to maintain the reflux. After complete addition of (A-3), the reflux is continued till all the magnesium turnings are reacted. The reaction mass is then cooled to room temperature, trifluoroacetaldehyde gas is passed through the Grignard reagent solution at a certain slow rate. The reaction mass is stirred at room temperature. After completion of the reaction, reaction mass is poured on cold saturated solution of ammonium chloride and extracted with solvents like Ethyl acetate. The organic layer is separated. The aqueous layer is washed with solvent. The combined organic layer is washed with brine, dried over anhydrous sodium sulfate, and is filtered and concentrated under vacuum conditions to give a hydroxy intermediate which is used for next step without purification.

[0151] The next step comprises flask fitted with apparatus including but not limited to surface condenser, thermometer pocket, thermometer, stirrer and is charged with hydroxy intermediate dissolved in acetone and cooled. Jones’ reagent is then added till the deep brown red color persisted in the reaction mass. The reaction is then filtered, concentrated under reduced pressure to obtain a residue. The residue is dissolved in ethyl acetate and organic layer washed with water, brine, dried over anhydrous sodium sulfate, and is filtered and concentrated under reduced pressure to obtain l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-l-one (A-4). After purification, purity and yields are calculated. Purity is found to be above 94%, and yield above 88%.

[0152] In another embodiment, the process of preparation of 3 -Methylacetophenone (B-2), comprises a reactor fitted with apparatus including but not limited to double surface condenser, thermometer pocket, thermometer, stirrer is charged with solvent like ethylene dichloride (EDC) which is followed by acetophenone (B-l). A lewis acid including but not limited to A1CE is added under vigorous stirring. After complete addition of lewis acid, methylating agent is introduced using deep pipe into the reaction mixture under stirring. It is important to exercise caution that the deep pipe does not get chocked due to lewis acid slurry (such as Aluminium chloride slurry). The reaction is heated at temperature about 50-65° C for 10-20 Hrs. After the completion of the reaction, the reaction mass is cooled, and slowly poured on crushed ice with vigorous stirring. The organic layer is separated using separatory apparatus (including but not limited to funnel). Aqueous layer is washed with EDC. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 3 -Methylacetophenone (B-2). After purification, purity and yield are calculated and purity is found to be atleast above 96%, Yield is found to be atleast above 71 % In another embodiment, the process of preparation of 4'-Bromo-3 '-methylacetophenone (B-3) comprises a reactor fitted with different apparatus including but not limited to condenser, thermometer pocket, thermometer, stirrer, guard tube is charged with an acid and 3- Methylacetophenone (B-2) followed by a suitable catalyst including but not limited to Ferric bromide. The reaction mass is stirred well. The reaction is carried out in hood. Halogenating agent is dissolved in acid and is added dropwise under stirring. After complete addition of halogenating agent, the reaction mass is stirred at temperature 55-75° C for about 7-11 Hrs. Unreacted halogenating agent is quenched with sodium sulfite solution and then the acid from the reaction mass is distilled out at reduced pressure. The residue is poured on 5-15% aqueous solution of base and is extracted with EDC. The organic layer is separated and the aqueous layer is washed with EDC. The combined organic layer is washed with water, brine, and is dried over anhydrous sodium sulfate, is filtered and concentrated under reduced pressure to furnish 4'-Bromo-3'-methylacetophenone (B-3). After purification, purity and yield are calculated. Purity is found to be above 95%, and yield is found to be above 69 %.

[0153] In another embodiment, the process for preparation of 4-Acetyl-2-methylbenzoic acid (B-4) comprises a flask fitted with different apparatus including but not limited to the thermometer pocket, thermometer, stirrer and is charged with 4'-Bromo-3'-methylacetophenone (B-3) dissolved in solvents like dry THF . The reaction is blanketed with gas including but not limited to nitrogen. The reaction is charged and conducted under complete Nitrogen atmosphere in order to avoid moisture penetration. The reaction mass is cooled upto -85° C using dry-ice and solvent like acetone. Base including but not limited to A-butyl lithium (n-BuLi) is added using pump over 30 mins - 1 hr. The reaction mass becomes darker in color. Carbon dioxide is added in small portions and the reaction mass is stirred at around -70 to -85°C for about 20-40 mins and is allowed to warm. As the reaction progresses, the deep darker color is changed to lighter color. After completion of the reaction, the reaction mass is carefully poured on ice-cold saturated solution of ammonium chloride , and is acidified to pH below 7 and is extracted with suitable solvent like ethyl acetate. The layers are separated and aqueous layer is washed with solvent. The combined organic layer is washed with brine, dried over anhydrous sodium sulfate, and filtered and concentrated under reduced pressure to furnish 4-Acetyl-2- methylbenzoic acid (B-4). After purification, purity and yield are calculated and purity is found to be above atleast 97%, and yield is found to be atleast above 83 %. In another embodiment, the process for preparation of 4-Acetyl-2-methylbenzamide (B-5) comprises:

[0154] A reactor fitted different apparatus including but not limited to condenser, thermometer pocket, thermometer, stirrer, guard tube is charged with 4-Acetyl-2-methylbenzoic acid (B-4) is dissolved in solvents like ethylene dichloride (EDC) , followed by catalyst such as N,N- Dimethylformamide (DMF) at room temperature. Lewis acid (including but not limited to thionyl chloride (SOCh)) is added dropwise over 30 mins- 1 hr under vigorous stirring at room temperature. After complete addition of lewis acid, the reaction mass is refluxed (30 mins to 2 hrs) to ensure complete conversion of acid to the acid chloride. The reaction mass is cooled to rt and diluted with additional EDC. Aqueous ammonia solution is added. The complete reaction sequence is carried out in ventilated hood. After completion of the reaction, it is quenched by ice-cold water. The organic layer is separated. Aqueous layer is washed with EDC. The combined organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered and is concentrated under reduced pressure to furnish 4-Acetyl-2-methylbenzamide (B-5). After purification, purity and yield are calculated. Purity is found to be atleast above 96%, Yield is found to be atleast above 94 %.

[0155] In another embodiment, the process of preparation of 4-(2-Bromo-acetyl)-2-methyl- benzamide (B-6) comprises:

[0156] A reactor fitted with different apparatus including but not limited to condenser, thermometer pocket, thermometer, mechanical stirrer, guard tube (including but not limited to Calcium chloride guard tube) was charged with 4-Acetyl-2-methylbenzamide (B-5) dissolved in solvent such as ethylene dichloride (EDC) followed by Azobisisobutyronitrile (AIBN). Halogenating agent such as A- Bro mo succinimide (NBS) is added portion-wise at temperature in the range of 35-50 °C. After complete addition of NBS, the reaction mass is stirred for about 6-10 hr. After completion of the reaction, the reaction mass is filtered and the residue is washed with EDC. The combined filtrate is washed with water, brine, dried over anhydrous sodium sulfate, filtered and is concentrated at reduced pressure to furnish 4-(2-Bromo-acetyl)-2-methyl- benzamide. After purification, purity and yield are calculated and purity is found to be atleast above 91%, yield is found to be atleast above 74%.

[0157] In another embodiment, the process of preparation of 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-2-enoyl]-2-methylbenzamide (Formula 2) comprises:

[0158] A three necked flask fitted with different apparatus including but not limited to thermometer pocket, thermometer, mechanical stirrer is charged with solvent such as dry toluene followed by reagents for instance, but not limited to triphenylphosphine (PPh3) under nitrogen atmosphere. 4-(2-Bromo-acetyl)-2-methyl-benzamide (B-6) is dissolved in solvents like dry Tetrahydro furan (THF) in single lot at temperature closer to room temperature. Base such as Sodium methoxide (NaOMe) powder is added in 3-6 equal portions at room temperature. A deep yellow to brown colored reaction mass is observed. After complete addition of the base (sodium methoxide), the reaction mass is stirred for 10-20 mins followed by dropwise addition of l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-l-one (A-4) dissolved in solvents like toluene. The gradual decolorization of the reaction is seen indicating the reaction progress. After stirring for 1-3 hrs, the reaction is slowly poured on ice-cold brine solution. The organic layer is separated. Brine layer is washed with ethyl acetate (150 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 4-[(2E)- 3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl)-2-methylbenzamide [Formula (2)]. After purification, purity and yield are calculation. Purity is found to be above 92%, yield is found to be above 82%.

[0159] In another embodiment, the process of preparation of 4-[5-(3,5-Dichloro-phenyl)-5- (trifluoromethyl)-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide [Formula (3)] comprises:

[0160] A three necked flask fitted with different apparatus including but not limited to thermometer pocket, thermometer, mechanical stirrer is charged with aqueous solution of hydroxylamine hydrochloride in the presence of base (including but not limited to aqueous sodium hydroxide). This mixture is cooled. Intermediate (Compound of Formula (2) is dissolved in solvent (including but not limited to methanol) which is added dropwise without allowing the reaction temperature to rise above a certain temperature (around 8-12° C). After complete addition, the reaction mass is allowed to warm to room temperature and is stirred for 1-3 hrs. The reaction mass is cooled again to about 8-12° C, which is followed by acid mediated ring cyclization using acids comprising mineral acids for instance but not limited to HC1, H2SO4, HNO3, etc.. After complete addition, the reaction mass is allowed to warm upto room temperature and then heated to temperature above 70° C for 6-8 hrs. After completion of the reaction, the pH of the reaction mass is adjusted to value around 8 to obtain 4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide or 4-[5-(3,5-dichlorophenyl)- 5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2-methylbenzamide (Formula 3) as solid. The solid material is filtered, dried and recrystallized from solvent Isopropanol (IPA). After purification, purity and yield are calculated. The purity is found to be above 94%, and yield is found to be above 71%.

[0161] In another embodiment, the process for preparation of Fluxametamide of Formula (I), comprises:

[0162] A three necked flask fitted with different apparatus including but not limited to thermometer pocket, thermometer, mechanical stirrer, guard tube (including but not limited to anhydrous calcium chloride) is charged with formylating agent such as A,A-Dimethyl formamide (DMF). The flask is ice cooled and Phosphorous oxychloride is added dropwise. An exothermic reaction occurs and the phosphorus oxychloride-dimethylformamide complex is formed. After complete addition of POC13, the reaction mass is stirred for about 10-30 mins in ice bath followed by addition of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3- yl]-2-methyl-benzamide (3) dissolved in DMF. The reaction is allowed to warm to room temperature and then heated at temperature in range of 65-85° C for about 3-4 hours. After completion of the reaction, the reaction mass is poured carefully on crushed ice with continuous stirring. The pH of the solution is adjusted to 7-8 by addition of base such as sodium acetate. The product is extracted in solvent like ethyl acetate. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate, filtered and is concentrated to furnish the residue. The residue is dissolved in solvent like methanol and cooled in ice bath for about 8-9 hrs. Methoxylamine hydrochloride or Methoxy amine hydrochloride is added as a solid. To this mixture, base (including but not limited to sodium hydroxide) in water is added dropwise. The reaction is allowed to warm to room temperature and is stirred for 3-5 hr. After completion, the obtained solid is filtered and washed with water, followed by solvent (like toluene) to furnish crude Fluxametamide. The product is crystallized by using solvent such as 2-propanol, twice. After purification, purity and yield are calculated and purity is found to be above 97 %, yield is found to be above 83% .

[0163] The process for preparing Fluxametamide of formula (I) disclosed according to the present invention yields Fluxametamide of formula (I) with purity of around 96% to 99% and a yield of around above 83%.

[0164] According to another aspect, there is provided a process for preparing agrochemical composition comprising highly pure and stable Fluxametamide of formula (I) obtained as per the process disclosed herein. Yet in another embodiment, agrochemical compositions comprise at least a bio-active effective amount of highly pure and stable Fluxametamide of formula (I) obtained by the processes disclosed herein. The agrochemical compositions further contain one or more agrochemically acceptable excipients. Suitable excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and consideration of standard procedures and reference works in the field.

[0165] Although this invention has been disclosed in the context of certain preferred embodiments and examples, it will be understood by those skilled in the art that the present invention extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the invention and obvious modifications and equivalents thereof. Thus, from the foregoing description, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the invention as set forth herein.

[0166] It is to be understood that the present invention is susceptible to modifications, changes and adaptations by those skilled in the art. Such modifications, changes, adaptations are intended to be within the scope of the present invention.

[0167] Examples:

[0168] Example 1: Preparation of l,3-Dichloro-5-nitrobenzene (A-2)

[0169] A-1 A-2

[0170] Method A comprises: Ch (g), Ferric chloride (FeC13) / Nitrobenzene, 90- 100° C

[0171] Method B comprises: CI2 (g), Ferric chloride (FeCL), Acetic acid, Nitrobenzene, 110-120° C Method C comprises: A-Chlorosuccinimide (NCS), Ferric chloride (FeCL ), Acetic acid, 75- 85° C

[0172] Method A:

[0173] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, outlet tube. This outlet tube was connected to the chlorine gas quenching set up. Nitrobenzene (500 g, 4.06 mol), Ferric chloride (6.7 g, 0.04 mol) were charged into the reactor. The reaction mass was heated and maintained at 90-100° C. Chlorine gas (480 g, 6.5 mol) was slowly passed through in a such a way that no chlorine gas was escaping for 6-8 hrs. Then reaction was maintained at 90-100° C for 16 hrs. followed by cooling to room temperature rt. The reaction mass was diluted with Ethylene dichloride (EDC) (500 mL) and poured slowly over saturated sodium bicarbonate solution and stirred for 30 mins. The organic layer was separated. Aqueous layer was washed with EDC (200 mL). The combined organic layer washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish l,3-Dichloro-5-nitrobenzene (Intermediate A-2). After purification, HPLC purity (area): 95%, Yield: 484 g, 62%.

[0174] Method B:

[0175] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, outlet tube. This outlet tube was connected to the chlorine gas quenching set up. Acetic acid (250 mL) was charged to the reactor followed by Nitrobenzene (150 g, 1.22 mol), Ferric chloride (6 g, 0.04) and maintained at 110-120° C. Chlorine gas (141 g, 1.95) was slowly passed through in a such a way that no chlorine gas was escaping for 2-3 hrs. The reaction was maintained at 110-120° C for 16 hrs followed by cooling to room temperature (rt). The reaction mass was diluted with EDC (500 mL) and poured carefully over aqueous sodium hydroxide solution. The pH is adjusted to 8 and stirred for 30 mins. The organic layer was separated. Aqueous layer was washed with EDC (200 mL). The combined organic layer washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish l,3-Dichloro-5-nitrobenzene (Intermediate A-2). After purification, HPLC purity (area): 92%, Yield: 158 g, 67%.

[0176] Method C:

[0177] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Ethylene dichloride (EDC) (500 mL) was charged to the reactor followed by Nitrobenzene (153 g, 1.22 mol), Ferric chloride (6 g. 0.04 mol). The reaction mass was heated to 75-85° C and maintained. A-Chloro succinimide (NCS) (190.9 g, 1.4 mol) was added portion wise. The reaction was maintained at 75-85° C for 26 hrs. After completion of the reaction, the Succinimide formed was filtered. The residue was washed with EDC (2 X 100 mL). The combined organic layer washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to furnish l,3-Dichloro-5-nitrobenzene (Intermediate A-2). After purification, HPLC purity (area): 94%, Yield: 152 g, 65%. Example 2: Preparation of l-Bromo-3,5-dichlorobenzene (A-3)

[0178] A-2 A-3

[0179] In an autoclave reactor (2 Lit), l,3-Dichloro-5-nitrobenzene (Intermediate A-2) (131.6 g, 0.65 mol) was charged followed by Methanol (300 mL). 5% Pd / C (3.5 g) was charged carefully to this mixture. The autoclave was closed and then flushed with Nitrogen gas 3-4 times. Nitrogen gas was removed by applying a slight vacuum and then filled with Hydrogen gas. The pressure of hydrogen gas applied was 5 Kg / cm2. Stirring was started and continued. Whenever, the pressure of hydrogen drops below 5 Kg / cm2, hydrogen gas was refilled to make up the pressure. The reaction was monitored by TLC and HPLC. After completion of the reaction, hydrogen gas was vented out very carefully in water container. The reaction mass was filtered through celite and washed with methanol (2 X 50 mL). Combined methanolic layer was concentrated under vacuum to furnish 3,5-Dichloroaniline. Crude weight: 82.71 g. This crude material was used for the next step.

[0180] In a four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, 3,5-Dichloroaniline (82.5 g, 0.51 mol) was dissolved in hydrogen bromide (HBr) (296 g, 20% Aqueous, 0.51) and cooled to 0°C to 5° C. Sodium nitrite (34.22 g, 0.54 mol) dissolved in water was added dropwise without allowing the reaction mass temperature to rise above 5° C. After completion of the addition, the reaction was maintained at the same temperature for 30 mins. Cuprous bromide (CuBr)(77 g, 0.56) was added in lots at the same temperature. After addition of Cuprous bromide, the reaction was allowed to warm to room temperature and monitored by TLC and HPLC. Evolution of Nitrogen was seen. After completion, ethylene chloride (250 mL) was added and the organic layer was separated. The aqueous layer was washed with EDC (1 X 50 mL). The combined organic layer was washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish l-Bromo-3,5-dichlorobenzene (A-3). After purification, HPLC purity: 95%, yield: 74.3 g, 71%.

[0181] Example 3: Preparation of l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-l-one (A-4)

[0182] A-3 A-4

[0183] A four necked RB flask (500 mL) fitted with double surface condenser, thermometer pocket, thermometer, mechanical stirrer maintained under nitrogen atmosphere was charged with dry Tetrahydrofuran (THF) (110 mL), freshly activated magnesium turnings (7.85 g, 0.32 mol) and few crystals of iodine. A small aliquot (~5 mL) of l-Bromo-3,5-dichlorobenzene (A-3) (68.4 g, 0.29 mol) dissolved in dry THF (100 mL) was added. The reaction mass was slightly warmed to initiate the reaction. Once the formation of Grignard reagent set in, the remaining 1-Bromo- 3,5-dichlorobenzene (A-3) was added at a rate to maintain the reflux. After complete addition of l-Bromo-3,5-dichlorobenzene (A-3), the reflux was continued till all the magnesium turnings were reacted. The reaction mass was cooled to room temperature, trifluoroacetaldehyde gas (calculated quantity 45 g, 0.46 mol) was passed through the Grignard reagent solution at a very slow rate. The reaction mass was stirred at room temperature. After completion of the reaction, reaction mass was poured on ice-cold saturated solution of ammonium chloride and extracted with Ethyl acetate (300 mL). Organic layer was separated. Aqueous layer was washed with Ethyl acetate (2 X 50 mL). The combined organic layer washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give hydroxy intermediate (52.9 g) and used for next step without purification.

[0184] A four necked RB flask (500 mL) fitted with surface condenser, thermometer pocket, thermometer, mechanical stirrer was charged with hydroxy intermediate (52.5 g) dissolved in acetone (150 mL) and cooled to 0° C. Jones’ reagent was added dropwise till the deep brown red color persisted in the reaction mass. The reaction was filtered, concentrated under reduced pressure to afford a residue. The residue was dissolved in ethyl acetate (250 mL) and organic layer washed with water (2 X 100 mL), brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish l-(3,5-Dichlorophenyl)-2,2,2- trifluoroethan-l-one (A-4). After purification, HPLC purity: 95%, yield: 44.2 g, 89%.

[0185] Example 4: Preparation of 3-Methylacetophenone (B-2)

[0186] A four necked glass reactor (5 Lit) fitted with double surface condenser, thermometer pocket, thermometer, mechanical stirrer was charged with ethylene dichloride (EDC) (2500 mL) followed by acetophenone / 1-phenylethan-l -one (B-l)(360.5 g, 3 mol). Aluminium chloride (AICI3) (449 g, 3.3 mol) was added portion-wise under vigorous stirring. After complete addition of AICI3, methyl chloride gas (MeCI) (140 g, 2.7 mol) was introduced slowly using deep pipe into the reaction mixture under stirring. Caution was exercised that the deep pipe should not get chocked due to Aluminium chloride slurry. The reaction was heated at 55-60° C for 14 Hrs. After the completion of the reaction, the reaction mass was cooled to room temperature, and slowly poured on crushed ice with vigorous stirring in a well-ventilated fumehood. The organic layer was separated using separatory funnel. Aqueous layer was washed with EDC (200 mL). The combined organic layer was washed with water (2 X 500 mL), brine (300 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 3 -Methylacetophenone or l-(3-methylphenyl)ethan-l-one (B-2). After purification, HPLC purity: 97%, Yield: 289.9 g, 72 %

[0187] Example 5: Preparation of 4'-Bromo-3'-methylacetophenone (B-3)

[0188] Br2 / AcOH, FeBr3(cat) RT to 65° C

[0189] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube was charged with Acetic acid (150 mL) and 3- Methylacetophenone (B-2)(144.3 g, 1.04 mol) followed by Ferric bromide (FeBr3) (15.7 g, 0.05 mol). The reaction mass was stirred very well. The reaction was carried out in well- ventilated fume-hood. Bromine (187.2 g, 1.15 mol) dissolved in acetic acid (500 mL) was added dropwise under stirring. After complete addition of bromine, the reaction mass stirred at 65° C for 9 Hrs. Unreacted bromine was quenched with 10% sodium sulfite solution and then acetic acid from the reaction mass was distilled out at reduced pressure. The residue was poured on 10% Aqueous sodium hydroxide and extracted with EDC. The organic layer was separated and the aqueous layer was washed with EDC (100 mL). The combined organic layer was washed with water (2 X 500 mL), brine (300 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 4'-Bromo-3'-methylacetophenone (B-3). After purification, HPLC purity: 96%, Yield: 155.6 g, 70 %.

[0190] Example 6: Preparation of 4-Acetyl-2-methylbenzoic acid (B-4)

[0191] A three necked RB flask (500 mL) fitted with thermometer pocket, thermometer, mechanical stirrer was charged with 4'-Bromo-3 '-methylacetophenone (B-3) (52 g, 0.23 mol) dissolved in dry THF (100 mL). The reaction was blanketed with nitrogen to avoid any moisture penetration. The reaction mass was cooled to -78° C using dry-ice and acetone. A-butyl lithium (n-BuLi) (163 mL, 1.6 M solution in hexane, 0.26 mol) was added slowly using syringe pump over 45 mins. The reaction mass became dark brown in color. Solid carbon dioxide (21 g, 0.47 mol) was added in small portions and the reaction mass was stirred at -78°C for 30 mins and allowed to warm to room temperature. As the reaction progressed, the deep brown color changed to yellow to light yellow color. After completion of the reaction, the reaction mass was carefully poured on ice-cold saturated solution of ammonium chloride (100 mL), acidified to pH 5-6 and extracted with ethyl acetate (200 mL). The layers were separated and aqueous layer washed with ethyl acetate (2 X 100 mL). The combined organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 4-Acetyl-2-methylbenzoic acid (B-4). After purification, HPLC purity: 98%, Yield: 35.2 g, 84 %.

[0192] Example 7: Preparation of 4-Acetyl-2-methylbenzamide (B-5)

[0193] B-4 B-5

[0194] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube was charged with 4-Acetyl-2-methylbenzoic acid (B-4) (170.2 g, 0.90 mol) dissolved in ethylene dichloride (EDC) (350 mL), followed by A, A-Di methyl formamide (DMF) (1.34 g, 0.02 mol) at room temperature. Thionyl chloride (SOCI2) (119.91 g, 0.99 mol) was added dropwise over 45-50 mins under vigorous stirring at room temperature. After complete addition of thionyl chloride, the reaction mass was refluxed briefly (1 hr to 1.5 hr) to ensure complete conversion of acid to the acid chloride. The reaction mass was cooled to rt and diluted with additional EDC (350 mL). Aqueous ammonia solution was slowly added. The complete reaction sequence was performed in well ventilated fumehood. After completion of the reaction, it was quenched by pouring on ice-cold water. The Organic layer was separated. Aqueous layer was washed with EDC (100 mL). The combined organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 4-Acetyl-2-methylbenzamide (B-5). After purification, HPLC purity: 97%, Yield: 151.2g, 95 %.

[0195] Example 8: Preparation of 4-(2-Bromo-acetyl)-2-methyl-benzamide (B-6)

[0196] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube was charged with 4-Acetyl-2- methylbenzamide (B-5) (147.4 g, 0.79 mol) dissolved in EDC (500 mL) followed by AIBN (5.3 g, 0.03 mol). A-Bromo succinimide (NBS) (168.2 g, 0.87 mol) was added portion-wise at 40-45° C. After complete addition of NBS, the reaction mass was stirred for 8 hr. After completion of the reaction, the reaction mass was filtered and the residue was washed with EDC (100 mL). The combined filtrate was washed with water (1 X 150 mL), brine (1 X 150 mL), dried over anhydrous sodium sulfate, filtered and concentrated at reduced pressure to furnish 4-(2-Bromo-acetyl)-2-methyl-benzamide. After purification, HPLC purity: 92%, yield: 151.8 g, 75%. Example 9: Preparation of 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2- methylbenzamide (Formula (2))

[0197] A-4 B-6 (2)

[0198] A three necked RB flask (500 mL) fitted with thermometer pocket, thermometer, mechanical stirrer was charged with dry toluene (140 mL) followed by triphenylphosphine (PPh3)(68.8 g, 0.26 mol) under nitrogen atmosphere. 4-(2-Bromo-acetyl)-2-methyl-benzamide (B-6) (57.3 g, 0.21 mol) dissolved in dry Tetrahydrofuran (THF) (100 mL) was added in single lot at room temperature. Sodium methoxide (NaOMe) powder (12.5 g, 0.26 mol) was added in 4 equal portions at room temperature. A deep yellow to brown colored reaction mass was observed. After complete addition of sodium methoxide, the reaction mass was stirred for 15 mins followed by dropwise addition of l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-l-one (A-4) (52.6 g) dissolved in toluene (100 mL). The gradual decolorization of the reaction was seen indicating the reaction progress. After stirring for 2 hr, the reaction was slowly poured on ice- cold brine solution. The organic layer was separated. Brine layer was washed with ethyl acetate (150 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2- enoyl)-2-methylbenzamide (2). After purification, HPLC purity: 93%, yield: 68.7 g, 83%.

[0199] Example 10: Preparation of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl] -2-methyl-benzamide (3)

[0200] 1. NH2OH.HCI,

[0201] A three necked RB flask (500 mL) fitted with thermometer pocket, thermometer, mechanical stirrer was charged with aqueous solution of hydroxylamine hydrochloride (16.5 g in 20 mL water, 0.22 mol) followed by aqueous sodium hydroxide (9.8 g in 20 mL water, 0.24 mol). This mixture is cooled to 5 to 10° C. Intermediate (Compound of Formula (2) (87 g, 0.2 mol) dissolved in methanol (MeOH) (170 mL) was added dropwise without allowing the reaction temperature to rise above 10° C. After complete addition, the reaction mass was allowed to warm to room temperature and stirred for 2 hrs. The reaction mass was cooled again to 10° C and Hydrochloric acid (HC1) (67 g, 30%, 0.55 mol) was added slowly for acid mediated ring cyclization. After complete addition, the reaction mass allowed to warm to room temperature and then heated to 80° C for 7 hrs. After completion of the reaction, the pH of the reaction mass adjusted to 8 to obtain 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3- yl]-2-methyl-benzamide -(Formula 3) as solid. The solid material was filtered, dried and recrystallized from Isopropanol ( IPA). After purification, HPLC purity: 95%, yield: 60 g, 72%.

[0202] Example 11: Preparation of Fluxametamide (I)

[0203] A three necked RB flask (500 mL) fitted with thermometer pocket, thermometer, mechanical stirrer, anhydrous calcium chloride guard tube was charged A,A-Dimethyl formamide (DMF) (100 mL). The RB flask was ice cooled and Phosphorous oxychloride (24.8 g, 0.16 mol) was added dropwise. An exothermic reaction occurred with the formation of the phosphorus oxychloride-dimethylformamide complex. After complete addition of POC13, the reaction mass was stirred for 15 mins in ice bath followed by addition of 4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (3) (57.9 g, 0.13 mol) dissolved in DMF (150 ml). The reaction was allowed to warm to room temperature and then heated at 75-80° C for about 3.5 hrs. After completion of the reaction, the reaction mass was carefully poured on crushed ice with continuous stirring. The pH of the solution was adjusted to 7-8 by addition of sodium acetate. The product was extracted in ethyl acetate (350 mL). The organic layer was washed with water (2 X 150 mL), brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated to furnish N-Formyl-4-[5-(3,5-dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (54.6 g). (also referred as “residue”) The residue (as mentioned above) was dissolved in methanol (150 mL) and cooled in ice bath for about 8.5 hrs. Methoxylamine hydrochloride or Methoxy amine hydrochloride (11.9 g, 0.14 mol) was added as a solid. To this mixture, sodium hydroxide (5.7 g, 0.14 mol), in water (15 mL) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 4 hr. After completion, the obtained solid was filtered and washed with water, followed by toluene to furnish crude Fluxametamide. The product was crystallized from 2-propanol twice. After purification, HPLC purity: 97.6 %, yield: 52.4 g, 84%.

[0204] The present invention is more specifically explained by examples given above.

[0205] However, it should be understood that the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the present invention includes the given examples and further can be modified and altered without departing from the novel teachings and advantages of the invention which are intended to be included within the scope of the invention.

Claims

1.WE CLAIMClaim 1: A process for the preparation of Fluxametamide of Formula (I), comprising the steps of: i. reacting a compound of Formula A-4, namely l-(3,5-dichlorophenyl)-2,2,2- trifluoroethan-l-one, with a compound of Formula B-6, namely 4-(2-haloacetyl)-2- methylbenzamide, in the presence of a base and suitable solvent, to obtain a compound of Formula 2, namely 4-[(2E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]-2- methy Ibenzamide ; ii. reacting the compound of Formula 2 with hydroxylamine hydrochloride in the presence of a base and solvent, followed by acid-mediated cyclization, to obtain a compound of Formula 3, namely 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5- dihydro-l,2-oxazol-3-yl]-2-methylbenzamide; iii. formylating the compound of Formula 3, followed by reaction with methoxy amine hydrochloride to obtain Fluxametamide of Formula (I).Claim 2: A process for the preparation of the compound, l-(3,5-dichlorophenyl)-2,2,2- trifluoroethan-l-one of (Formula A-4) as claimed in claim 1, wherein the compound of Formula A-4 is obtained by the sequential reactions, comprising: i) reacting nitrobenzene of Formula A-l in the presence of halogenating agents, suitable solvents, to obtain a compound, l,3-dichloro-5-nitrobenzene of (Formula A-2); ii) converting l,3-dichloro-5-nitrobenzene of (Formula A-2) formed in step (i) to a compound, l-bromo-3,5-dichlorobenzene of (Formula A-3) by reduction and diazotization; iii) subjecting the compound of (Formula A-3) formed in step (ii) to oxidation in the presence of oxidizing agents, suitable solvents to obtain a compound, l-(3,5- dichlorophenyl)-2,2,2-trifluoroethan-l-one of (Formula A-4).Claim 3: A process for preparation of the compound, 4-(2-haloacetyl)-2-methy Ibenzamide of (Formula B-6) as claimed in claim 1, wherein the compound of Formula B-6 is obtained by the sequential reactions, which comprises: i. methylation of acetophenone (Formula B-l), in the presence of methylating agent, Lewis acid, suitable solvents to obtain a compound, 3 -Methylacetophenone of (Formulaii. mono-halogenating the aromatic ring of the compound of (Formula B-2) obtained in step (i) in the presence of suitable catalyst, halogenating agents to obtain a compound, 4'-Bromo-3'-methylacetophenone (Formula B-3); iii. reacting the compound of 4'-Bromo-3'-methylacetophenone (Formula B-3) obtained in step (ii) with base followed by reaction with carbon dioxide to obtain a compound, 4- acetyl-2-methylbenzoic acid of (Formula B-4). iv. converting the compound, 4-acetyl-2-methylbenzoic acid of (Formula B-4) obtained in step (iii) to corresponding acid chloride in the presence of the reagents, suitable solvents followed by amidation using suitable reagents to obtain a compound, 4-acetyl-2- methylbenzamide of (Formula B-5); v. converting the compound, 4-acetyl-2-methylbenzamide of (Formula B-5) obtained in step (iv) to the compound of 4-(2-bromoacetyl)-2-methylbenzamide of (Formula B-6), by halogenation.Claim 4: The process as claimed in claim 1, wherein the process of formylating the compound of Formula 3 in step (iii) is carried out in presence of formylating agent.Claim 5: The process as claimed in claim 1, wherein the process of acid mediated cyclization in step (ii) is carried out in presence of an acid selected from the group comprising inorganic acid, mineral acids, organic acids.Claim 6: The process as claimed in claim 2, wherein the oxidizing agent is selected from the group comprising MnCh, pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), Jones reagent or combination thereof.Claim 7 : The process as claimed in claim 3, wherein the corresponding acid chloride is obtained in the presence of the reagents selected from the group comprising from the group comprising thionyl chloride, sulfuryl chloride, phosphorous oxychloride, or combinations thereof.Claim 8 : The process as claimed in claim 3, wherein the suitable catalyst is selected from the group comprising 5-10% Pd on Charcoal or 5% Pt on Charcoal, ZSM-5, Cu(I) salts, trichloroisocyanuric acid (TCICA), Trifluoroacetic acid, Fe (III) salts, Aluminum chloride (A1C13), Ferric bromide (FeBn), Ferric chloride (FeCF), A,A-Dimethylformamide (DMF), Azobisisobutyronitrile (AIBN), trichloroisocyanuric acid (TCICA), or combination thereof.Claim 9 : The process as claimed in claim 3, wherein the methylating agent is selected from the group comprising methyl iodide, dimethyl sulfate, methyl chloride, methyl bromide, dimethylcarbonate, diazomethane, dimethyl amine, or combination thereof.Claim 10 : The process as claimed in claim 3, wherein the Lewis acid is selected from the group comprising Zinc chloride (ZnCh), Aluminium Chloride (A1CL), Ferric Chloride (FeCh), Boron Trifluoride (BF3), Boron Trichloride (BCI3), Titanium tetrachloride (TiCL), Antimony Pentafluoride (SbFs), Copper Chloride (CuCh), any metal triflates or Zeolites or combination thereof.Claim 11: The process as claimed in claims 1- 3, wherein the base is selected from the group comprising di-isopropylamine, diisopropylethylamine, tri-ethylamine, dimethylamine, trimethyl amine, pyridine, A- methyl morpholine, 3 -picoline, 2-picoline, 4-picoline, sodium hydroxide, potassium hydroxide, n-butyl lithium, sodium carbonate, sodium bicarbonate, sodium acetate, potassium carbonate, or their bicarbonate salts, calcium hydroxide, sodium methoxide (NaOMe) or combination thereof.Claim 12: The process as claimed in claim 3, wherein the halogenation is carried out in the presence of halogenating agent.Claim 13: The process as claimed in claims 2-3, 12, wherein the halogenating agent is selected from the group comprising chlorine gas, A-chlorosuccinimidc (NCS), Thionyl chloride, phosphorus pentachloride, phosphorus tribromide, hydrogen bromide, hydrogen peroxide, X2, HX, wherein X = Cl, Br, I, sulfuryl chloride, phosphorus trichloride, A- Bro mo succinimide (NBS), in combination with acetic acid, H2O2, potassium, and H2SO4 or combination thereof.Claim 14: The process as claimed in claim 3, wherein the amidation is carried by the suitable reagents selected from the group comprising ammonia gas, or aqueous ammonia or ammonium acetate or ammonium formate or combination thereof.Claim 15: The process as claimed in claims 1, 4, wherein the formylating agent is selected from the group comprising para-formaldehyde, formalin, formic acid, methyl formate, N,N- dimethylformamide (DMF), Phosphorous oxychloride, diazomethane, cyanogen bromide, hydrogen cyanide or combination thereof.Claim 16: The process as claimed in claims 1-3, wherein the suitable solvents are selected from the group comprising ethylene chloride, ethylene dichloride (EDC), methylene dichloride (MDC), chlorobenzene, methanol, ethyl acetate, acetic acid, A,A-dimethylformamide (DMF), benzene, chloroform, 1, 4-dioxane, diethyl ether, acetic acid, hydrogen peroxide, o- dichlorobenzene, carbon tetrachloride, chlorobenzene, dichlorobenzene, tetrahydrofuran (THF) and acetonitrile, ethyl acetate, acetone, dimethylsulfoxide, cyclohexane, hexane, heptane, toluene, xylene, Isopropanol (IPA), 2-propanol, Phosphorous oxychloride, water, brine, sodium sulfate or combination thereof.Claim 17: The process for the preparation of Fluxametamide of Formula (I), as claimed in claims (1-16), wherein the Fluxametamide of Formula (I) is obtained in free form or in agrochemically acceptable salt or in formulation form.Claim 18: A process for preparing an agrochemical composition comprising Fluxametamide of Formula (I) as obtained by the process claimed in claims 1-17.Claim 19: An agrochemical composition, wherein the composition comprises at least a bioactive effective amount of Fluxametamide of Formula (I) as obtained by the process claimed in claims 1-17.Claim 20: The agrochemical composition as claimed in claim 19, which further comprises one of more agrochemically acceptable excipients.Claim 21: A process for preparing the agrochemical composition comprising Fluxametamide of Formula (I) as claimed in claims 19-20.

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