Process for preparation of optically active fluxametamide

Abstract

The present invention relates to a process for the preparation of an optically active 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 an optically active 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 an optically active Fluxametamide of formula (I) of the present invention.

Description

[0001] PROCESS FOR PREPARATION OF OPTICALLY ACTIVE FLUXAMETAMIDE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a process for the preparation of an optically active 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] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the present invention, or that any publication specifically or implicitly referenced is prior art.

[0006] Fluxametamide belongs to the isoxazoline insecticides, and it is developed and produced as a racemate by Nissan Chemical Industries, Ltd. It has a chemical name as 4-((57?S)-5-(3,5- dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole-3-yl)-A-((E'Z)- (methoxyimino)methyl)-o-toluamide, having the structural formula as below Formula (II):

[0007] Formula (I) Formula (II)

[0008] (S)-(+)-Fluxametamide Fluxametamide

[0009] Fluxametamide has broad- spectrum bioactivity to many kinds of pests, including Lepidoptera, Acarina, Thysanoptera, and Diptera. These pests are harmful to vegetables, such as cabbage, Chinese cabbage, cotton, tea plant, and soybean. Fluxametamide is a novel type of ligand gated chloride channel (LGCC) antagonist, which mainly affects y-aminobutyric acid-gated chloride channel (GABACls) of pests with novel mode of action. Thus, the application of fluxametamide could help delay the development of insecticide resistance, and it has been in the registration process in several countries.

[0010] Prior art documents are known which discloses the synthesis of racemic isoxazoline derivative compounds, for instance: U.S. Patent No. 7,662,972 discloses the compound of Formula (II) and synthesis of various isoxazoline-substituted benzamide compounds. The prior art discloses the use of toxic reagents like carbon monoxide thereby 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. Thus, the process in the prior art is more polluting, makes use of toxic and hazardous chemicals and special purpose equipments which makes it economically unattractive and also more polluting as compared to the process of the current invention, which on contrary does neither utilize / produce such toxic gases nor incorporate such hazardous chemical. Thus, the disclosed process in the prior art is economically less viable. The prior art also does not disclose synthesis of optically active Fluxametamide which is crucial substance of the present invention.

[0011] Further, 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. Secondly, this prior art does not teach the resolution of the desired intermediate and thereby the synthesis of chiral Fluxametamide.

[0012] Synthesis of optically active Fluxametamide is not reported to the best of our knowledge. Therefore, it is desirable to provide economical, less hazardous, easy and commercially viable process for the production of optically pure isoxazoline-substituted benzamide compound, Fluxametamide of Formula (I).

[0013] Moreover, many European countries have introduced pesticide taxes to reduce pesticide input and environmental load, which would facilitate the development and use of highly effective and low-risk enantiomers of chiral pesticides. It has been shown that for many racemic agrochemical and pharmaceutical compounds, only one enantiomer is biologically active, or that one enantiomer is significantly more active than the other enantiomer. For optimal efficacy, lower application rate in the field, increased selectivity, favorable toxicological and ecological safety, improved user-friendliness and better cost-effectiveness, only one active isomer of the racemic agrochemical is always desired.

[0014] Asymmetric synthesis either by a chiral induction or resolution of racemates is employed to synthesize the active isomer of the racemic agrochemical.

[0015] Therefore, it is a need for a process for preparation of chirally pure and active Fluxametamide.; therefore, the present invention conceived a process for the preparation of chiral (5)-(+)- Fluxametamide of formula (I) by using chiral reagents to resolve the intermediate carboxylic acid to ensure chiral separation of desired enantiomer and thereby synthesis of (5)-(+)- Fluxametamide (Formula 1). 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 novel process for the preparation of optically active 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N- [(methoxyamino) methylene] -2-methylbenzamide chemically known as Fluxametamide in free form or in agrochemically acceptable salt or in formulation form starting from readily accessible and more economic intermediates which are easy to handle, which process makes it possible to prepare an optically active Fluxametamide of formula I in a simple manner and good yield.

[0018] Another objective of the present invention is to provide novel process for the preparation of optically pure 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N- [ (methoxy aminojmethylene] -2-methylbenzamide chemically known as Fluxametamide in free form or in agro chemically acceptable salt which can be further used for formulating into suitable dosage forms.

[0019] Another objective of the present invention is to provide a process for the preparation of an optically active Fluxametamide of Formula (I), in simple manner and in good yield.

[0020] Another objective of the present invention is to provide the process to obtain a cleaner product with minimum or no by-products formation.

[0021] Another objective of the present invention is to provide the process for the preparation of an optically active Fluxametamide of formula (I), its intermediates and process of preparation of intermediates involving milder conditions like moderate temperature and pressure.

[0022] Another objective of the present invention is to provide an industrially and economically robust process with safe operations.

[0023] Another objective of the present invention is to obtain a key intermediate (C-l), methyl 4- [(2EZ)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate, by the coupling reaction between a compounds (A-3), i.e., l-(3-chloro-5-nitrophenyl)-2,2,2- trifluoroethan-l-one, and (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate using the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Horner reaction.

[0024] Another objective of the present invention is to obtain an intermediate dihydroisoxazole (C-2), z.e., methyl 4-[5-(3-chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate by cyclizing the key intermediate (C-l), z.e., methyl 4-[(2Z)-3-(3-chloro-5- nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate, in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using the suitable solvent to further obtain a chirally pure Fluxametamide.

[0025] Another objective of the present invention is to obtain a compound (C-3), i.e., 4-[5-(3,5- dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2-methylbenzoic acid, by hydrogenating the dihydroisoxazole compound (C-2) in the presence of hydrogen and catalysts or by transfer hydrogenation either at atmospheric pressure or in autoclave up to 50 Bar pressure and solvents to yield the corresponding aniline, i.e., Methyl 4-[5-(3-Amino-5-chloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoatewhich is further diazotized under standard conditions followed by treatment with CuCl and hydrolysis.

[0026] Another objective of the present invention is to obtain an enantiomer intermediate (C-4), by chirally resolving the racemic compound (C-3), by the resolution techniques in the presence of a resolving agents like chiral amine or chiral alcohols. The diastereomeric salt thus formed after treating the acid (C-3) with the chiral amine of interest is recrystallized from the suitable solvent to obtain the desired enantiomer of the acid (C-3) which is freed from salt by treating the salt with acid to get the desired enantiomer the acid (C-4). Alternatively, the diastereomeric ester thus formed after treating the acid (C-3) with chiral alcohol in the presence of acid is hydrolyzed to get the desired enantiomer of the acid (C-4). The acid for hydrolysis of ester can be selected from organic or inorganic acids.

[0027] Another objective of the present invention is to obtain an intermediate (S)-4-[5-(3,5-Dichloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (compound C-5) by converting the enantiomer of the acid (compound C-4) to a corresponding benzamide, followed by formylation using phosphorous oxychloride and N, A-Di methyl formamide (DMF).

[0028] Another objective of the present invention is to obtain a compound Fluxametamide of Formula (I) by treating the compound C-5 with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0029] Some or all these and other objects of the invention can be achieved by way of the invention described hereinafter.

[0030] ADVANTAGES OF THE PRESENT INVENTION:

[0031] 1. The present invention provides a process and intermediates with enhanced regioselectivity, thereby improving the efficiency and consistency of the synthetic route.

[0032] 2. The disclosed process results in a significantly improved yield of the desired end product, making it suitable for commercial and industrial-scale applications.

[0033] 3. The process offers a cleaner product profile, with minimal or no formation of undesirable by-products, thereby reducing the need for extensive purification and minimizing environmental burden.

[0034] 4. The process, intermediates, and the methods for preparing said intermediates are carried out under mild conditions, including moderate temperature and pressure, thereby enhancing operational safety and reducing energy consumption.

[0035] 5. The process is industrially scalable, economically viable, and amenable to safe handling and operations, making it highly suitable for commercial manufacturing environments.

[0036] SUMMARY OF THE INVENTION

[0037] Accordingly, the main aspect of the present invention is to provide novel process for the preparation of optically active 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3- isoxazolyl]-N-[(methoxyamino) methylene] -2-methylbenzamide chemically known as Fluxametamide in free form or in agrochemically acceptable salt or in formulation form starting from readily accessible and cheap intermediates which are easy to handle, which process makes it possible to prepare Fluxametamide of formula (I) in a simple manner and good yield.

[0038] Another aspect of the present invention is to provide novel process for the preparation of optically pure 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N- [ (methoxy aminojmethylene] -2-methylbenzamide chemically known as Fluxametamide in free form or in agrochemically acceptable salt which can be further used for formulating into suitable dosage forms. Another aspect of the present invention is to provide a process for the preparation of an optically active Fluxametamide of Formula (I), in simple manner and in good yield.

[0039] Another aspect of the present invention is to provide the process for the preparation of an optically active Fluxametamide of formula (I), its intermediates and process of preparation of intermediates having an improved regio selectivity.

[0040] As per the principles of organic chemistry and basis of chiral resolution, when a racemate is resolved by resolution, one of the diastereomers is formed in a major proportion. That contributes to the regio selectivity. The present invention has shown to possess improved regioselectivity. In an aspect, the present invention provides a process for the preparation of optically pure Fluxametamide of Formula (I), wherein, the said process comprises the steps of: i. coupling a compound (A-3), z.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one and (B-4), z.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate uisng the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Horner reaction, to obtain an intermediate (C-l), i.e., methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4- trifluorobut-2-enoyl]-2-methylbenzoate; ii. cyclizing an intermediate (C-l), in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield dihydroisoxazole compound (C-2), z.e., methyl 4-[5-(3-chloro-5-nitrophenyl)-5- (trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3-yl] -2-methylbenzoate; iii. hydrogenating the dihydroisoxazole (C-2), in the presence of hydrogen and catalysts using suitable solvent to yield the corresponding aniline (Methyl 4-[5-(3-Amino-5- chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoate) which is further diazotized under standard conditions followed by treatment with CuCl, and hydrolysis to obtain a compound (C-3), i.e., 4-[5-(3,5-dichlorophenyl)-5- (trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3-yl] -2-methylbenzoic acid; iv. resolving the racemic compound (C-3) in the presence of a resolving agents to obtain a diastereomeric salt which in turn is recrystallized from the suitable solvent followed by release of free acid by treating the diastereomeric salt with the suitable acid to obtain an enantiomer of the acid (C-3), i.e., (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl- 4,5-dihydro-isoxazol-3-yl]-2-methylbenzoic acid (C-4) ; and v. converting the chiral acid (C-4) to the corresponding benzamide followed by formylation using phosphorous oxychloride and A,A-Dimethylformamide (DMF) and then followed by treatment with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0041] In another aspect, the present invention provides a key intermediate (C-l), i.e., methyl 4-[(2Z)- 3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate, obtained by the coupling reaction between a compounds (A-3), i.e., l-(3-chloro-5-nitrophenyl)-2,2,2- trifluoroethan-l-one, and (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate using the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Horner reaction.

[0042] In another aspect, the present invention provides an intermediate dihydroisoxazole (C-2), i.e., methyl 4-[5-(3-chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate, obtained by cyclizing the key intermediate (C-l), i.e., methyl 4-[(2Z)-3-(3- chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate, in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using the suitable solvent to further obtain a chirally pure Fluxametamide.

[0043] In another aspect, the present invention provides a compound (C-3), i.e., 4-[5-(3,5- dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2-methylbenzoic acid, obtained by hydrogenating the dihydroisoxazole compound (C-2) in the presence of hydrogen and catalysts or by transfer hydrogenation either at atmospheric pressure or in autoclave up to 50 Bar pressure and a suitable solvent to yield the corresponding aniline (i.e., Methyl 4-[5-(3- Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoate) which is further diazotized under standard conditions followed by treatment with CuCl and hydrolysis.

[0044] In another aspect, the present invention provides an enantiomer intermediate (C-4), that is obtained by resolving the racemic compound (C-3), by the resolution techniques in the presence of a resolving agents like chiral amine or chiral alcohols. The diastereomeric salt thus formed after treating the acid (C-3) with the chiral amine of interest is recrystallized from the suitable solvent to obtain the desired enantiomer of the acid (C-3) which is freed from salt by treating the salt with acid to get the desired enantiomer the acid (C-4). Alternatively, the diastereomeric ester thus formed after treating the acid (C-3) with chiral alcohol in the presence of acid is hydrolyzed to get the desired enantiomer of the acid (C-4). In another aspect, the present invention provides a process for preparing an optically active compound Fluxametamide of Formula (I) by converting the chiral acid (C-4) to the corresponding benzamide followed by formylation using phosphorous oxychloride and N,N- Dimethylformamide (DMF) and then followed by treatment with methoxyamine hydrochloride.

[0045] In another aspect, the present invention provides a process to prepare an intermediate (S)-4-[5- (3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (compound C-5) by converting the enantiomer of the acid (compound C-4) to a corresponding benzamide, followed by formylation using phosphorous oxychloride and N,N- Dimethylformamide (DMF).

[0046] In another aspect, the present invention provides a process to prepare an optically active compound Fluxametamide of Formula (I) by treating the compound C-5 with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0047] DETAILED DESCRIPTION OF THE INVENTION

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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:

[0053] The articles “a” and “an” are used herein to refer to one or to more than one (i.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.

[0054] 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.

[0055] 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.

[0056] While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention.

[0057] 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.

[0058] Conventional methods for the preparation of Fluxametamide are associated with drawbacks such as use of toxic reagents like carbon monoxide, special equipments which are not easy to operate with no suggestion of high purity. Further, these conventional processes and equipments make the process uneconomical.

[0059] 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.

[0060] It is to be understood by one of the ordinary skilled in the art that the present discussion is description of exemplary embodiments only and is not to be construed as limiting the broader aspects of the present invention.

[0061] In an embodiment, the present invention provides a process for the preparation of optically pure Fluxametamide of Formula (I), wherein, the said process comprises the steps of: a) coupling a compound (A-3), z.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one and (B-4), z.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate using the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Horner reaction, to obtain an intermediate (C-l), i.e., methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4- trifluorobut-2-enoyl]-2-methylbenzoate; b) cyclizing an intermediate (C-l), in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield dihydroisoxazole compound (C-2), z.e., methyl 4-[5-(3-chloro-5-nitrophenyl)-5- (trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3-yl] -2-methylbenzoate; c) hydrogenating the dihydroisoxazole (C-2), in the presence of hydrogen and catalysts in the presence of solvents to yield the corresponding aniline (i.e., Methyl 4-[5-(3-Amino- 5-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoate) which is further diazotized under standard conditions followed by treatment with CuCl, and hydrolysis to obtain a compound (C-3), i.e., 4-[5-(3,5-dichlorophenyl)-5- (trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3-yl] -2-methylbenzoic acid; d) resolving the racemic compound (C-3) in the presence of resolving agents to obtain a diastereomeric salt which in turn is recrystallized from the suitable solvent followed by release of free acid by treating the diastereomeric salt with the suitable acid to obtain an enantiomer of the acid (C-3), i.e., (C-4); and e) Converting the chiral acid (C-4) to the corresponding benzamide followed by formylation using phosphorous oxychloride and A,WDimethylformamide (DMF) and then followed by treatment with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0062] In one of the embodiments, the key intermediate (C-l), z.e., methyl 4-[(2Z)-3-(3-chloro-5- nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate, is obtained by the coupling reaction between a compounds (A-3), z.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l- one, and (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate using the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Homer reaction (Scheme 1).

[0063] In one of the embodiments, the compound (A-3) is obtained by sequential reactions starting from Nitrobenzene (A-l) (Scheme 2), wherein, nitrobenzene (A-l) is subjected to acylation in the presence of acylating agent and Lewis acids to furnish the compound (A-2), i.e., 2,2,2- trifluoro- l-(3-nitrophenyl)ethan- l-one.

[0064] In an embodiment, the compound (A-2) is halogenated in the presence of halogenating agent to furnish a compound (A-3), i.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one. In one of the embodiments, the halogenating agent is chlorinating agent.

[0065] In one of the embodiments, a compound (B-4), i.e., methyl 4-(2-bromoacetyl)-2- methylbenzoate is obtained by sequential reactions from o-Xylene (B-l) (Scheme 3), wherein, o-Xylene (B-l) is subjected to acylation in the presence of an acylating agent and Lewis acids to furnish a compound (B-2), i.e., l-(3,4-dimethylphenyl)ethan-l-one.

[0066] In an embodiment, the compound (B-2) was protected as ketal followed by oxidation under controlled conditions known to the person skilled in the art provides the corresponding acid i.e., 4-Acetyl-2-methyl-benzoic acid which is converted to the acid chloride in the presence of halogenating agents followed by treatment with suitable alcohol to furnish a compound (B-3), i.e., methyl 4-acetyl-2-methylbenzoate.

[0067] In an embodiment, the compound (B-3) is subjected to halogenation in the presence of halogenating agent and a suitable solvent to provide a compound (B-4), i.e., methyl 4-(2- bromoacetyl)-2-methylbenzoate. In one of the embodiments, the halogenating agent is brominating agent.

[0068] In one of the embodiments, the key intermediate obtained is converted into chirally pure Fluxametamide by the series of the transformations (Scheme 4), the key intermediate (C- 1), i.e., methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2- methylbenzoate is cyclized in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield dihydroisoxazole (C-2), i.e., methyl 4- [5-(3-chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate.

[0069] In an embodiment, the dihydroisoxazole (C-2) is hydrogenated in the presence of hydrogen and catalysts or by transfer hydrogenation either at atmospheric pressure or in autoclave up to 50 Bar pressure and solvents to yield the corresponding aniline (i.e., Methyl 4-[5-(3-Amino-5- chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoate) which is further diazotized under standard conditions followed by treatment with CuCl and hydrolysis to provide a compound (C-3), i.e., 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3 -yl] -2-methylbenzoic acid.

[0070] In an embodiment, the racemic compound (C-3) is resolved using the resolution techniques known to the skilled person in the art. Further, the compound (C-3) is resolved using the resolving agents like chiral amine or chiral alcohols. The diastereomeric salt thus formed after treating the acid (C-3) with the chiral amine of interest is recrystallized from the suitable solvent to obtain the desired enantiomer of the acid (C-3) which is freed from salt by treating the salt with acid to get the desired enantiomer the acid (C-4).

[0071] In an embodiment, the diastereomeric ester thus formed after treating the acid (C-3) with chiral alcohol in the presence of acid is hydrolyzed to get the desired enantiomer of the acid (C-4).

[0072] In one of the embodiments, the desired chiral acid (C-4) is converted to the corresponding benzamide followed by formylation using phosphorous oxychloride and N,N- Dimethylformamide (DMF) and then followed by treatment with methoxyamine hydrochloride to furnish a target compound, Fluxametamide of Formula (I).

[0073] In another embodiment, (compound C-4) is converted to the corresponding benzamide, followed by formylation using phosphorous oxychloride and N, A-Di methyl formamide (DMF) which is then followed by treatment with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0074] In an embodiment, is the present invention provides a process for the preparation of an optically active Fluxametamide of Formula (I), wherein, the process comprising the following steps: The key intermediate (C-l), i.e., methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut- 2-enoyl]-2-methylbenzoate for synthesizing Fluxametamide is obtained by the coupling reaction between a compound (A-3), i.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l- one and (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate using the reaction like but not limited to Wittig reaction or modified Wittig reaction or Witting Horner reaction (Scheme 1).

[0075] Scheme 1:

[0076] Compound (A-3), i.e., l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one is obtained by sequential reactions starting from Nitrobenzene (A-l) (Scheme 2). When Nitrobenzene (A-l) is subjected to acylation using trifluoroacetic anhydride or trifluoroacetic acid in the presence of Lewis acids like but not limited to Aluminium chloride, Zinc Chloride, Ferric chloride, any metal triflates or Zeolites and alike to furnish a compound (A-2), i.e., 2,2,2-trifluoro-l-(3- ni trophcny I Jcthan- 1 -one.

[0077] N°2

[0078] ^fCF3

[0079] 0

[0080] A-2

[0081] Compound (A-2) is chlorinated using chlorinating agents like but not limited Chlorine gas or Chlorine in acetic acid or A-Chlorosuccinimidc or alike to furnish a compound (A-3), i.e., 1- (3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan- 1 -one.

[0082] A-3

[0083] Scheme 2:

[0084] Compound (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate is obtained by sequential reactions from o-Xylene (B-l) (Scheme 3). When o-Xylene (B-l) is subjected to acylation in the presence of Acetyl chloride or Acetic anhydride in the presence of Lewis acids like but not limited to Aluminium chloride, Zinc Chloride, Ferric chloride, any mineral acids including but not limited to hydrochloric acid, Sulfuric acid (H2SO4), Nitric acid (HNO3), etc., any metal triflates or Zeolites and alike to furnish the compound (B-2), i.e., l-(3,4-dimethylphenyl)ethan- 1-one.

[0085] B-2

[0086] Compound (B-2) after protection as ketal, under controlled oxidative conditions known to the person skilled in the art provides the corresponding acid i.e., 4-Acetyl-2-methyl-benzoic acid which is converted to the acid chloride in the presence of chlorinating agents like but not limited to Thionyl chloride, Oxalyl chloride, Phosphorous trichloride or phosphorous pentachloride in Methyl alcohol to furnish compound (B-3), i.e., methyl 4-acetyl-2-methylbenzoate.

[0087] Scheme 3:

[0088] The compound (B-3) is subjected to bromination using brominating agents like aqueous HBr & H2O2, KBr, H2O2 & H2SO4 or A-bromosuccinimidc (NBS) and alike in the suitable solvent and radical initiator including but not limited to Azobisisobutyronitrile (AIBN), Benzoyl peroxide to provide a compound (B-4), i.e., methyl 4-(2-bromoacetyl)-2-methylbenzoate. The key intermediate thus obtained is converted into chirally pure Fluxametamide by the series of the transformations (Scheme 4).

[0089] Scheme 4:

[0090] Scheme 4:

[0091] (S)-(+)-Fluxamitamide

[0092] C20H16CI2F3N3O3

[0093] Mol. Wt: 474.26 The key intermediate (C-l) i.e., methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2- enoyl]-2-methylbenzoate is converted to the corresponding oxime, using hydroxylamine hydrochloride in the suitable solvent followed by acid mediated ring closure to yield dihydroisoxazole (C-2), i.e., methyl 4-[5-(3-chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5- dihydro-l,2-oxazol-3-yl]-2-methylbenzoate. The corresponding oxime is formed in-situ and is converted to the isooxazoline intermediate C-2.

[0094] Dihydroisoxazole (C-2) is hydrogenated using hydrogen and catalysts like 5-10% Pd on Charcoal or 5%Pt on Charcoal or by transfer hydrogenation either at atmospheric pressure or in autoclave up to 50 Bar pressure in solvents like methanol, ethanol, 2-propanol, ethyl acetate, acetic acid or alike to yield the corresponding aniline (i.e., Methyl 4-[5-(3-Amino-5-chloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoate) which is further diazotized under standard conditions followed by treatment with CuCl and hydrolysis to provide a compound (C-3), i.e., 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro- 1 ,2-oxazol-3 -yl] -2-methylbenzoic acid.

[0095] The compound (C-3) is resolved using the resolution techniques known to the skilled person in the art. Further, the compound (C-3) is resolved using the resolving agents like chiral amine or chiral alcohols. The chiral amines like but not limited to (R)-(+)-a-Methylbenzylamine, (S)- (-)-a-Methylbenzylamine, (S)-(+)- 1 -Cyclohexylethylamine, (R)-(+)-a,4-

[0096] Dimethylbenzylamine, (R)-(+)-a-Ethylbenzylamine, (S)-(-)-a-Ethylbenzylamine (R)-4- Fluoro-a-methylbenzylamine, and alike are employed as resolving agents for the said resolution. The diastereomeric salt thus formed after treating the acid (C-3) with the chiral amine of interest is recrystallized from the suitable solvent including but not limited to Methanol, 2-propanol, tert. -Butanol, THF, Ethyl acetate and alike. The desired enantiomer of the acid (C-3) is freed from salt by treating the salt with acid to get the desired enantiomer of the acid (C-4).

[0097] The chiral alcohols like but not limited to (S)-(+)-2-Butanol, (R)-(-)-2-Butanol, (S)-(-)-2- Methyl-1 -butanol, (S)-(+)-2-Octanol, (R)-(-)-2-Octanol, (R)-(+)-l -Phenylethylalcohol, (S)-(- )-l -Phenylethylalcohol, (R)-(-)-l-Phenyl-2,2,2-trifluoroethanol, (S)-(+)-l-Phenyl-2,2,2- trifluoroethanol and alike are employed for the said resolution. The diastereomeric ester thus formed after treating the acid (C-3) with chiral alcohol in the presence of acid is hydrolyzed to get the desired enantiomer of the acid (C-4).

[0098] The desired chiral acid (C-4) is converted to the corresponding benzamide followed by formylation using phosphorous oxychloride and A,A-Dimethylformamide (DMF) followed by treatment with Methoxy amine hydrochloride furnishes Fluxametamide (I).

[0099] In one of the embodiments, the acylating agent is selected from the group comprises of Trifluoroacetyl chloride or trifluoroacetic anhydride or trifluoroacetic acid or acetyl chloride, or mixture thereof.

[0100] In one of the embodiments, the Lewis acids is selected from the group comprises of Zinc chloride (ZnCh), Aluminium Chloride (AICI3), Ferric Chloride (FeCL), Boron Trifluoride (BF3), Boron Trichloride (BCI3), Titanium tetrachloride (TiCL), Antimony Pentafluoride (SbFs), Thionyl chloride (SOCI2), Copper Chloride (CuCh), mineral acids such as hydrochloric acid, Sulfuric acid (H2SO4), Nitric acid (HNO3), etc., any metal triflates or Zeolites or mixtures thereof.

[0101] In one of the embodiments, the halogenating agent is selected from the group comprises of Chlorine gas or Chlorine in acetic acid or N-Chlorosuccinimide, Thionyl chloride, Oxalyl chloride, Phosphorous trichloride or phosphorous pentachloride, HBr & H2O2, KBr, H2O2 and H2SO4 or N-bromo succinimide (NBS) or mixtures thereof. In an embodiment, the halogenating agent is selected from chlorinating agent or brominating agent.

[0102] In one of the embodiments, the solvent is selected from the group comprises of Ethylene chloride, Ethylene dichloride (EDC), Methylene dichloride (MDC), Chlorobenzene, methanol, ethanol, 2-propanol, tert-butyl alcohol, n-butyl alcohol, .vec-butyl alcohol, ethyl acetate, acetic acid, A,iV-dimethylformamide, benzene, chloroform, 1, 4-dioxane, diethyl ether, acetic acid, o- dichlorobenzene, carbon tetrachloride, chlorobenzene, dichlorobenzene, tetrahydrofuran and acetonitrile, , Acetone, dimethylsulfoxide, cyclohexane, hexane, heptane, toluene, xylene, water or mixtures thereof.

[0103] In one of the embodiments, the formylating agent is selected from the group comprises of paraformaldehyde, formalin, formic acid, methyl formate, N, A-di methyl formamide, diazomethane, cyanogen bromide, or mixture thereof in the presence of other reagents including but not limited to phosphorous oxychloride.

[0104] In one of the embodiments, the catalysts used in the present invention are selected from the group comprises of 5-10% Pd on Charcoal or 5%Pt on Charcoal or Raney-Nickel, Azobisisobutyronitrile (AIBN), Benzoyl peroxide, ZSM-5, Cobalt (II) acetylacetone [(Co(acac)2], Tctra-n-butyl ammonium bromide (TBAB) or mixtures thereof.

[0105] 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, potassium carbonate, or their bicarbonate salts, calcium hydroxide, Sodium methoxide , sodium acetate, or combination thereof.

[0106] In one of the embodiments, the chiral amine is selected from the group comprises of (R)-(+)- a-Methylbenzylamine, (S)-(-)-a-Methylbenzylamine, (S)-(+)-l-Cyclohexylethylamine, (R)- (+)-a,4-Dimethylbenzylamine, (R)-(+)-a-Ethylbenzylamine, (S)-(-)-a-Ethylbenzylamine (R)- 4-Fluoro-a-methylbenzylamine or mixtures thereof.

[0107] In one of the embodiments, the chiral alcohol is selected from the group comprises of (S)-(+)- 2-Butanol, (R)-(-)-2-Butanol, (S)-(-)-2-Methyl-l-butanol, (S)-(+)-2-Octanol, (R)-(-)-2- Octanol, (R)-(+)-l -Phenylethylalcohol, (S)-(-)-l-Phenylethylalcohol, (R)-(-)-l-Phenyl-2,2,2- trifluoroethanol, (S)-(+)-l-Phenyl-2,2,2-trifluoroethanol or mixtures thereof.

[0108] In one of the embodiments, the process for preparing an optically active Fluxametamide of formula (I), gave Fluxametamide with purity of 95% to 99% and a yield of above 80%.

[0109] In one of the embodiments, the process for the preparation of optically active Fluxametamide of Formula (I) affords the desired enantiomer with a chemical purity in the range of 95% to >99%, and an enantiomeric (chiral) purity ranging from 95% to 98%, thereby enabling the isolation of highly pure and enantiomeric ally enriched product suitable for agrochemical applications.

[0110] In one of the embodiments, the process of preparation of optically pure Fluxametamide of Formula (I), wherein, the said process comprises the steps of: i. coupling l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A-3), with methyl 4-(2-bromoacetyl)-2-methylbenzoate (compound B-4), to obtain methyl 4- [(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate (intermediate C-l); ii. cyclizing the intermediate (C-l), in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield methyl 4-[5-(3- chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate (dihydroisoxazole compound (C-2)); iii. hydrogenating the dihydroisoxazole compound (C-2), in the presence of hydrogen and suitable catalysts, or by transfer hydrogenationat atmospheric pressure or up to 50 Bar pressure using suitable solvent to yield a corresponding aniline, (Methyl 4-[5-(3- Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl- benzoate) followed by diazotization and treatment with cuprous chloride (CuCl) and hydrolysis to obtain 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2- oxazol-3-yl]-2-methylbenzoic acid (compound C-3), wherein the compound C-3 is a racemic compound; iv. resolving the racemic compound (C-3) in the presence of resolving agent(s) selected from chiral amines or chiral alcohols, to obtain a diastereomeric salt or diastereomeric ester; v. recrystallizing the diastereomeric salt or ester obtained in step (iv) from the suitable solvent, followed by release of free acid by treatment of the diastereomeric salt or ester with acid to obtain an enantiomer of the acid (compound C-4); vi. converting the enantiomer of the acid (compound C-4) obtained in step (v), to a corresponding benzamide 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzamide, followed by formylation using phosphorous oxychloride and A-Di methyl formamide (DMF) to obtain (compound C-5); vii. treating the compound C-5; with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0111] In one of the embodiments, an alternative process of obtaining the enantiomer of the acid (C- 4) as claimed in claim 1, which comprising treating the compound (C-3) with the suitable chiral alcohol in the presence of acid to obtain a diastereomeric ester, which is further hydrolyzed to obtain the enantiomer of the acid (C-4).

[0112] In one of the embodiments, the process for the preparation of the compound (A-3), comprising: i. subjecting nitrobenzene (A-l) to acylation in the presence of acylating agent and Lewis acids to obtain 2,2,2-trifluoro-l-(3-nitrophenyl)ethan-l-one (compound A-2); ii. halogenating the compound (A-2) as obtained in step (i) in the presence of halogenating agent to obtain l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A-3).

[0113] In one of the embodiments, the process for the preparation of methyl 4-(2-bromoacetyl)-2- methylbenzoate (compound B-4), comprising: i. subjecting a compound (o-Xylene) (B-l) to acylation in the presence of an acylating agent and Lewis acids to obtain l-(3,4-dimethylphenyl)ethan-l-one (compound B-2); ii. protecting the compound (B-2) as ketal derivative (i.e., 2-(3,4-Dimethyl-phenyl)-2- methyl-[l,3] dioxolane), followed by oxidation under controlled conditions to obtain a corresponding acid, i.e., 4-Acetyl-2-methyl-benzoic acid ; iii. converting the corresponding acid obtained in step (ii) to acid chloride, 4-Acetyl-2- methylbenzoyl chloride in the presence of halogenating agents followed by treatment with suitable alcohol, to furnish methyl 4-acetyl-2-methylbenzoate (compound B-3); iv. subjecting the compound (B-3) obtained in step (iii) to halogenation in the presence of halogenating agent and suitable solvent to provide a compound (B-4), i.e., methyl 4-(2- bromoacety 1) -2 -methylbenzoate .

[0114] In one of the embodiments, the acylating agent is selected from the group comprises of Trifluoroacetyl chloride or trifluoroacetic anhydride or trifluoroacetic acid, acetyl chloride, acetic anhydride or combination thereof.

[0115] In one of the embodiments, the Lewis acid is selected from the group comprises of Zinc chloride (ZnCh), Aluminium Chloride (A1CL), Ferric Chloride (FeCL), Boron Trifluoride (BF3), Boron Trichloride (BCI3), Titanium tetrachloride (TiCL), Antimony Pentafluoride (SbFs), Thionyl chloride (SOCI2), Copper Chloride (CuCh), mineral acids such as hydrochloric acid, Sulfuric acid (H2SO4), Nitric acid (HNO3), etc., any metal triflates or Zeolites or combination thereof.

[0116] In one of the embodiments, the halogenating agent is selected from a chlorinating agent or a brominating agent or combination thereof.

[0117] In one of the embodiments, the chlorinating agent is selected from the group comprising Chlorine gas or Chlorine in acetic acid or A-Chlorosuccinimide, Thionyl chloride, Oxalyl chloride, Phosphorous trichloride or phosphorous pentachloride in Methyl alcohol or combination thereof. In one of the embodiments, the brominating agent is selected from the group comprising aqueous HBr & H2O2, KBr, H2O2 & H2SO4 or A-bromosuccinimidc (NBS) or combination thereof.

[0118] In one of the embodiments, the halogenating agent is further selected from the group comprising Chlorine gas or Chlorine in acetic acid or N-Chlorosuccinimide, Thionyl chloride, Phosphorous trichloride or phosphorous pentachloride, HBr & H2O2, KBr, H2O2 and H2SO4 or N-bromo succinimide (NBS) or combination thereof.

[0119] In one of the embodiments, the suitable solvent is selected from the group comprises of Ethylene chloride, Ethylene dichloride (EDC), Methylene dichloride (MDC), Chlorobenzene, methanol, ethanol, 2-propanol, tert-butyl alcohol, n-butyl alcohol, .vec-butyl alcohol, ethyl acetate, acetic acid, A,A-di methyl formamide (DMF), benzene, chloroform, 1, 4-dioxane, diethyl ether, acetic acid, o-dichlorobenzene, carbon tetrachloride, chlorobenzene, dichlorobenzene, tetrahydrofuran and acetonitrile, Acetone, dimethylsulfoxide, cyclohexane, hexane, heptane, toluene, xylene, Isopropanol / 2-propanol, water, brine, sodium sulphate or water combination thereof.

[0120] In one of the embodiments, the formylating agent is selected from the group comprises of paraformaldehyde, formalin, formic acid, methyl formate, N, A-di methyl formamide, diazomethane, cyanogen bromide, or combination thereof in the presence of other reagents such as phosphorous oxychloride.

[0121] In one of the embodiments, the suitable catalyst is selected from the group comprises of 5-10% Pd on Charcoal or 5% Pt on Charcoal or Raney-Nickel, ZSM-5, radical initiators including Azobisisobutyronitrile (AIBN), Benzoyl peroxide, ZSM-5, Cobalt (II) acetylacetone [(Co(acac)2], Tetra-n-butyl ammonium bromide (TBAB), and , phase transfer catalysts like quaternary ammonium or phosphonium salts or combination thereof.

[0122] In one of the embodiments, the acid is selected from the group comprising of organic or inorganic acid or combination thereof.

[0123] In one of the embodiments, the organic or inorganic acid is selected from the group comprising of hydrochloric acid (HC1), Sulfuric acid (H2SO4), Nitric acid (HNO3), phosphoric acid, orthophosphoric acid, acetic acid, propanoic acid, p-Toluene sulfonic acid (p-TSA), benzene sulfonic acid, methane sulfonic acid or combination thereof.

[0124] In one of the embodiments, the chiral amine is selected from the group comprises of (R)-(+)- a-Methylbenzylamine, (S)-(-)-a-Methylbenzylamine, (S)-(+)-l -Cyclohexylethylamine, (R)- (+)-a,4-Dimethylbenzylamine, (R)-(+)-a-Ethylbenzylamine, (S)-(-)-a-Ethylbenzylamine (R)- 4-Fluoro-a-methylbenzylamine or combination thereof.

[0125] In one of the embodiments, the chiral alcohol is selected from the group comprises of (S)-(+)- 2-Butanol, (R)-(-)-2-Butanol, (S)-(-)-2-Methyl-l-butanol, (S)-(+)-2-Octanol, (R)-(-)-2- Octanol, (R)-(+)-l -Phenylethylalcohol, (S)-(-)-l-Phenylethylalcohol, (R)-(-)-l-Phenyl-2,2,2- trifluoroethanol, (S)-(+)-l-Phenyl-2,2,2-trifluoroethanol or combination thereof.

[0126] In one of the embodiments, the suitable alcohol is selected from methyl alcohol (methanol), ethanol, 2-propanol, tert-butyl alcohol, n-butyl alcohol, sec-butyl alcohol or combination thereof.

[0127] In one of the embodiments, the process for preparing agrochemical composition comprising optically pure Fluxametamide of Formula (I) as obtained by the process disclosed in the present invention.

[0128] In one of the embodiments, an agrochemical composition, wherein the composition comprises at least a bio-active effective amount of optically pure Fluxametamide of Formula (I) disclosed in the present invention.

[0129] In one of the embodiments, the agrochemical composition further comprises one of more agrochemically acceptable excipients.

[0130] In one of the embodiments, the process for preparing the agrochemical composition comprising optically pure Fluxametamide of Formula (I) as disclosed in the present invention.

[0131] Below are the references for the compounds involved in the process of the present invention:

[0132] A-l: Nitrobenzene;

[0133] A-2: 2,2,2-trifluoro-l-(3-nitrophenyl)ethan- 1-one or 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone;

[0134] A-3: l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one or l-(3-Chloro-5-nitro-phenyl)- 2,2,2-trifluoro-ethanone;

[0135] B-l: o-xylene;

[0136] B-2: l-(3,4-dimethylphenyl)ethan-l-one or l-(3,4-Dimethyl-phenyl)-ethanone;

[0137] B-3: methyl 4-acetyl-2-methylbenzoate;

[0138] B-4: methyl 4-(2-bromoacetyl)-2-methylbenzoate;

[0139] C-l: methyl 4-[(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate or Methyl 4- [3 -(3 -Chloro-5-nitro-phenyl)-4,4,4-trifluoro-but-2-enoyl] -2-methylbenzoate ;

[0140] C-2: methyl 4-[5-(3-chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-

[0141] 2-methylbenzoate or 4-[5-(3-Chloro-5-nitro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-

[0142] 3-yl]-2-methyl-benzoic acid methyl ester;

[0143] C-3: 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoic acid or 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3- yl]-2-methyl-benzoic acid;

[0144] C-4: Enantiomeric form of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2- oxazol-3-yl]-2-methylbenzoic acid or S-(+)- 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl- 4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid;

[0145] C-5: ( S ) - 4 - [5-(3 ,5-Dichloro-phenyl)-5 -trifluoromethyl-4,5-dihydro-isoxazol-3 -yl] -2-methyl- benzamide;

[0146] Formula (I): (S)-(+)- Fluxametamide

[0147] In one of the embodiments, the process for the preparation of optically pure Fluxametamide of Formula (I), wherein, the said process comprises the steps of: i. coupling l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A-3), with methyl 4-(2-bromoacetyl)-2-methylbenzoate (compound B-4), to obtain methyl 4- [(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate (intermediate C-l); ii. cyclizing the intermediate (C-l), in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield methyl 4-[5-(3- chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate (dihydroisoxazole compound (C-2)); iii. hydrogenating the dihydroisoxazole compound (C-2), in the presence of hydrogen and suitable catalysts, or by transfer hydrogenation at atmospheric pressure or up to 50 Bar pressure using a suitable solvent to yield a corresponding aniline (i.e., Methyl 4-[5-(3- Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl- benzoate), followed by diazotization and treatment with cuprous chloride (CuCl) and hydrolysis to obtain 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2- oxazol-3-yl]-2-methylbenzoic acid (compound C-3), wherein the compound C-3 is a racemic compound; iv. resolving the racemic compound (C-3) in the presence of resolving agent(s) selected from chiral amines or chiral alcohols, to obtain a diastereomeric salt or diastereomeric ester; v. recrystallizing the diastereomeric salt or ester obtained in step (d) from the suitable solvent, followed by release of free acid by treatment of the diastereomeric salt or ester with acid to obtain an enantiomer of the acid (compound C-4); vi. converting the enantiomer of the acid (compound C-4) to a corresponding benzamide, followed by formylation using phosphorous oxychloride and A-Di methyl formamide (DMF) to obtain (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzamide (compound C-5); vii. treating the compound C-5; obtained in step (g) with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).

[0148] In one of the embodiments, the process for resolving the racemic compound (C-3) comprises treating the compound (C-3) with the suitable chiral alcohol in the presence of suitable acid in catalytic quantity to obtain a diastereomeric ester, which is further hydrolyzed to obtain the enantiomer of the acid (C-4). The acid for the esterification can be either organic or inorganic acid.

[0149] In one of the embodiments, the process for the preparation of the compound (A-3), comprising: i. subjecting nitrobenzene (A-l) to acylation in the presence of acylating agent and Lewis acids to obtain 2,2,2-trifluoro-l-(3-nitrophenyl)ethan-l-one (compound A-2); ii. halogenating the compound (A-2) as obtained in step (i) in the presence of halogenating agent to obtain l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A- 3).

[0150] In one of the embodiments, the process of preparation of 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone (A-2), comprises two methods, Method A; Method B.

[0151] In one of the embodiments, the process of preparation of 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone (A-2), wherein, Method A comprises:

[0152] A reactor fitted with different apparatus such as condenser, thermometer pocket, thermometer, mechanical stirrer, is charged with suitable solvent followed by nitrobenzene (A-l). Suitable catalyst is added. Acylating agent such as Trifluoroacetic anhydride is added dropwise over 20-40 mins and then the reaction mass is refluxed for 7-10 hrs. After completion of the reaction, the reaction mass is filtered and the filtrate is poured slowly over base such as sodium bicarbonate solution and stirred for 20-40 mins. The organic layer is separated. Aqueous layer is washed with suitable solvent. The combined organic layer is washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish 2,2,2-Trifluoro-l-(3-nitro- phenyl)-ethanone (A-2). After purification, purity is found to be above 94%, and yield if found to be above, 76%.

[0153] In one of the embodiments, the process of preparation of 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone (A-2), wherein, Method B comprises:

[0154] A reactor (2 Lit) fitted with different apparatus such as condenser, thermometer pocket, thermometer, mechanical stirrer, is charged with suitable solvent followed by nitrobenzene (A- 1). Suitable catalyst is added. Acylating agent is added dropwise over 30mins -1 hr and then the reaction mass is refluxed for duration of 15-20 hrs. After completion of the reaction, the reaction mass is filtered and the filtrate is poured slowly over saturated sodium bicarbonate solution and stirred for 20-40 mins. The organic layer is separated. Aqueous layer is washed with suitable solvent. The combined organic layer is washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone (A-2). After purification, purity is found to be above 94%, and yield is found above 63 %.

[0155] In one of the embodiments, the process of preparation of l-(3-Chloro-5-nitro-phenyl)-2,2,2- trifluoro-ethanone (A-3), comprises:

[0156] A pressure reactor is charged with suitable solvent followed by 2,2,2-Trifluoro-l-(3-nitro- phenyl)-ethanone (A-2). Lewis acid including but not limited to Anhydrous ferric chloride is added. The reactor is filled with halogenating agent and the pressure of halogenating agent is held in the range of 4-7 Bar. The reaction is heated to 100-140° C for 14-18 hrs under constant stirring. After completion of the reaction, the excess halogenating agent is quenched. Suitable solvent is added to the reaction mass and it is poured slowly over base such as aqueous sodium hydroxide and stirred for 20-40mins. The organic layer is separated. Aqueous layer is washed with suitable solvent. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish l-(3-Chloro-5-nitro-phenyl)- 2,2,2-trifluoro-ethanone (A-3). After purification, purity is found to be above 94%, yield is found to be above 62%.

[0157] In one of the embodiments, the process of preparation of l-(3,4-Dimethyl-phenyl)-ethanone (B-2), comprises:

[0158] A reactor fitted with different apparatus such as condenser, thermometer pocket, thermometer, mechanical stirrer, calcium chloride guard tube, and is charged with suitable solvent which is followed by o-Xylene (B-l) and lewis acid including but not limited to Aluminum chloride. The mixture is cooled to temperature range of 5-15° C. Acylating agent is added dropwise over 30 mins - 1 hr under vigorous stirring. After complete addition of acylating agent, the reaction mass is allowed to warm to room temperature and stirred for 3-4.5 hrs. After completion of the reaction, the reaction mass is slowly poured over ice-cold mineral acid (including but not limited to HC1). After complete quenching, the mass is brought to room temperature. Organic layer is separated. The aqueous layer is washed with suitable solvent. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish) l-(3,4-Dimethyl-phenyl)-ethanone (B-2). After purification, purity is found to be above 91%, and yield is found to be above 75%.

[0159] In one of the embodiments, the process of preparation of Methyl 4-Acetyl-2-methyl-benzoate (B-3), comprises:

[0160] A reactor fitted with different apparatus comprising condenser, thermometer pocket, thermometer, mechanical stirrer, calcium chloride guard tube and is charged with suitable solvent followed by l-(3,4-Dimethyl-phenyl)-ethanone (B-2), Reagent such as Monoethylene glycol (MEG), and acid such as p-Toluenesulfonic acid (p-TSA). The reaction mass is heated to 65-80° C for 6-8 hrs. After completion of the reaction, the reaction mass is cooled to room temperature, quenched with addition of water. The organic layer is separated and washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 2-(3,4-Dimethyl-phenyl)-2-methyl-[l,3]dioxolane (ketal derivative of B-2). The weight of crude material. The crude material is used without further purification for the next conversion. A pressure reactor is charged with suitable solvent followed by 2-(3,4-Dimethyl-phenyl)-2- methyl-[ 1,3] dioxolane followed by Cobalt (II) acetylacetone [(Co(acac)2], Tetra-n-butyl ammonium bromide (TB AB). The pressure reactor is closed. The stirring is started. The reactor is flushed twice with oxidizing agent including but not limited to oxygen. The reactor is filled with oxygen and pressure is taken to 2-5 bar. The reactor is heated to 100-120° C. After attaining the temperature, pressure of oxidizing agent (oxygen) is elevated up to 12 Bar. The reaction is continued for 8-10 hrs till completion. After completion of the reaction, the reactor is cooled down to room temperature, excess oxidizing agent (oxygen) is bubbled through water before opening of the reactor. Suitable solvent is distilled out and the residue is poured on ice- cold base such as NaOH solution. The aqueous layer is washed with suitable solvent. The aqueous layer is acidified with mineral acid (including but not limited to concentrated HC1) at lower temperature. The solid obtained is filtered and dried till constant weight to furnish 4- Acetyl-2-methyl-benzoic acid. Purification is performed and the purity is found to be above 97%, and yield is found to be above 68%.

[0161] Further, a reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube is charged with 4-Acetyl-2-methyl-benzoic acid dissolved in suitable solvent including but not limited to methanol, followed by A,A / -Di methyl formamide (DMF) at room temperature. Halogenating agent is added dropwise over 30 mins to 1 hr under vigorous stirring at 0° C to 10° C. After complete addition of halogenating agent, the reaction mass is warmed to room temperature and then refluxed briefly to ensure complete conversion of acid to the ester. The reaction mass is cooled to rt and solvent is removed under vacuum. The residue is diluted with suitable solvent. Water is added. The Organic layer is separated. Aqueous layer is washed with suitable solvent. The combined organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish Methyl 4-Acetyl-2-methyl-benzoate (B-3). After purification, purity is found to be above 96%, yield is found to be above 84%.

[0162] In one of the embodiments, the process of preparation of Methyl 4-(2-Bromo-acetyl)-2- methylbenzoate (B-4), comprises:

[0163] A reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube is charged with Methyl 4-Acetyl-2-methyl-benzoate (B-3) dissolved in suitable solvent followed by radical initiator including but not limited to AIBN. Halogenating agent is added portion-wise at 35-50° C. After complete addition of halogenating agent, the reaction mass is stirred for 7-9 hr. After completion of the reaction, the reaction mass is filtered and the residue is washed with suitable solvent. The combined filtrate is washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated at reduced pressure to furnish Methyl 4-(2-Bromo-acetyl)-2-methylbenzoate (B-4). After purification, purity is found to be above 94%, and yield above 75%.

[0164] In one of the embodiments, the process of preparation of Methyl 4-[3-(3-Chloro-5-nitro- phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methylbenzoate (C- 1), comprises:

[0165] A glass reactor fitted with thermometer pocket, thermometer, mechanical stirrer is charged with suitable solvent followed by reagent such as triphenylphosphine under nitrogen atmosphere. Methyl 4-(2-Bromo-acetyl)-2-methylbenzoate (B-4) dissolved in suitable solvent is added in single lot at room temperature. Base including but not limited to Sodium methoxide powder is added in several equal portions at room temperature. A deep yellow to brown colored reaction mass is observed. After complete addition of sodium methoxide, the reaction mass is stirred for 10-30 mins followed by dropwise addition of l-(3-Chloro-5-nitro-phenyl)-2,2,2-trifluoro- ethanone (A-3) dissolved in suitable solvent. The gradual decolorization of the reaction is seen indicating the reaction progress. After stirring for 1.5-3 hr, the reaction is slowly poured on cooled brine solution. The organic layer is separated. Brine layer is washed with suitable solvent. The combined organic layer is dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish Methyl 4-[3-(3-Chloro-5-nitro-phenyl)-4,4,4- trifluoro-but-2-enoyl]-2-methylbenzoate (C-l). After purification, purity is found to be above 96%, yield is found to be above 79%.

[0166] In one of the embodiments, the process of preparation of 4-[5-(3-Chloro-5-nitro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (C-2), comprises:

[0167] A reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, is charged with aqueous solution of hydroxylamine hydrochloride followed by aqueous sodium hydroxide. This mixture is cooled to 0 to 12° C. Intermediate (C-l) dissolved in suitable solvent is added dropwise without allowing the reaction temperature to rise above certain point. After complete addition, the reaction mass is allowed to warm to room temperature and stirred for 1- 3 hrs. The reaction mass is cooled again to 5-15° C and acid (including but not limited to mineral acid) is added slowly. After complete addition, the reaction mass is allowed to warm to room temperature and then heated to 70-90° C for 6-8 hrs. After completion of the reaction, the pH of the reaction mass adjusted to 7.5-8.5 to obtain 4-[5-(3-Chloro-5-nitro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (C-2) as solid. The solid material is filtered, dried and recrystallized from Isopropanol (IPA). After purification, purity is found to be above 95%, yield is found to be above 74%.

[0168] In one of the embodiments, the process of preparation of 4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid (C-3), comprises three steps:

[0169] Step 1: In an autoclave reactor 4-[5-(3-Chloro-5-nitro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (C-2) is charged followed by suitable solvent. Catalyst including but not limited to 5% Pd / C is charged carefully to this mixture. The autoclave is closed and then flushed with Nitrogen gas 3-4 times. Nitrogen gas is removed by applying a slight vacuum and then filled with Hydrogen gas. The pressure of hydrogen gas applied is up to 7 Kg / cm2. Stirring is started and continued. Whenever, the pressure of hydrogen drops below certain point value, hydrogen gas is refilled to make up the pressure. After completion of the reaction, hydrogen gas is vented out very carefully in water container. The reaction mass is filtered through celite and washed with suitable solvent such as methanol. Combined methanolic layer is concentrated under vacuum to furnish 4-[5-(3-Amino-5-chloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester. Crude weight: 86.2 g. This crude material is used for the next step.

[0170] Step 2: In reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Reagent such as Sodium nitrite dissolved in water is added dropwise to acid including but not limited to mineral acid without allowing the reaction mass temperature to rise above a certain point. To this nitrous acid solution, 4-[5-(3-Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester dissolved in suitable solvent is added dropwise over 1-2 hr at 0°C to 10° C. After completion of the addition, the reaction is maintained at the same temperature for 20-40 mins. Cuprous chloride is added in lots at the same temperature. After addition of Cuprous chloride, the reaction is allowed to warm to room temperature and monitored by TLC and HPLC. Evolution of Nitrogen is seen. After completion, solvent such as ethylene chloride is added and the organic layer is separated. The aqueous layer is washed with suitable solvent. The combined organic layer is washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish 4-[5- (3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester. After purification, purity is found to be above 94%, yield is found to be above 75%.

[0171] Step 3:

[0172] A reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, is charged with suitable solvent followed by 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (200 g). This is stirred to make homogenous solution. To this solution, base including but not limited to aqueous sodium hydroxide is added in a single lot. The reaction is stirred at room temperature for 5-8 hrs to get a clear solution. The reaction is monitored by HPLC. After 5-8 hrs, the reaction is complete and the reaction mass is cooled to room temperature. The reaction mass is acidified till pH 4.5- 6.5 by using acid including but not limited to mineral acid (HC1) to obtain solid. The solid thus obtained is filtered, dried till constant weight. Purity is found to be above 96%, yield is found to be above 88%.

[0173] In one of the embodiments, the process of preparation of S-(+)- 4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid, S-(+)-(C-4) by resolution, comprises:

[0174] A flask fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, is charged with 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl- benzoic acid dissolved in suitable solvent. (S)-(-)-a-Methylbenzylamine dissolved in solvent (such as THF) is added dropwise. The diastereomeric salt as solid is separated out. The mixture is briefly heated for 20-45 mins and filtered. The solid residue is washed with suitable solvent. The solid material is recrystallized from suitable solvent such as ethanol. This diastereomeric salt is neutralized with acids including but not limited to HC1 to give the desired enantiomer. The chiral purity of the enantiomer is determined using HPLC machine with DAD detector, at room temperature. Mobile phase of MeOH / Formic Acid mixture is pumped at a certain flow rate.

[0175] Retention time of (S)-(C-4) acid is determined with chiral purity above 97 %.

[0176] The above filtrate is concentrated to furnish the another diastereomeric salt (S,R). After recrystallization, the salt is neutralized with acid including but not limited to HC1 to give (R)- (C-4) acid.

[0177] Retention time of (R)-(C-4) acid is determined and and chiral purity is found to be above 91 %. In one of the embodiments, the process of preparation of (S)-4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide, (C-5), comprises:

[0178] A flask fitted with thermometer pocket, thermometer, mechanical stirrer, anhydrous calcium chloride guard tube is charged with a solution of S-(+)- 4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid in suitable solvent. N,N- Dimethylformamide is added as a catalyst. Thionyl chloride is added dropwise. After complete addition, the reaction mass is refluxed briefly to ensure complete reaction. After completion of the reaction, the reaction mass is cooled to +10- 15° C and reagent such as aqueous ammonia is added dropwise. The reaction mass is then stirred at room temperature for 3-4 hrs. The reaction mass is diluted with suitable solvent. The organic layer is separated and washed successively with water, brine, dried over anhydrous sodium sulfate and filtered. The organic layer is concentrated to furnish (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzamide, (C-5). After purification, purity is found to be above: 96%, yield si found to be above 94%.

[0179] In one of the embodiments, the process of preparation of (S)-(+)-Fluxametamide, comprises: A flask fitted with thermometer pocket, thermometer, mechanical stirrer, anhydrous calcium chloride guard tube is charged with formylating agent such as N, A-Di methyl formamide (DMF). The RB flask is ice cooled and Phosphorous oxychloride is added dropwise. An exothermic reaction occurs with the formation of the phosphorus oxychloride -dimethylformamide complex. After complete addition of POCh, the reaction mass is stirred for 10-20 mins in ice bath followed by addition of (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]- 2-methyl-benzamide dissolved in suitable solvent. The reaction was allowed to warm to room temperature and then heated at 70-90° C. After completion of the reaction, the reaction mass is carefully poured on crushed ice with continuous stirring. The pH of the solution is adjusted to 7-8 by addition of sodium acetate. The product is extracted in suitable solvent. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to furnish the residue.

[0180] The residue is dissolved in suitable solvent and cooled in ice bath. Methoxylamine hydrochloride is added as a solid. To this mixture, base such as sodium hydroxide in water is added dropwise. The reaction is allowed to warm to room temperature and stirred for 4 hr. After completion, the obtained solid is filtered and washed with water, followed by suitable solvent to furnish crude (S)-(+)-Fluxametamide. The product is crystallized from suitable solvent twice. After purification, purity is found to be above 98 %, Chiral purity is found to be above 98 %, Retention time RT is found to be about 8 min, yield is found to be above: 86 %.

[0181] 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.

[0182] Accordingly, it is not intended that the scope of the foregoing description be limited to the description set forth above, but rather that such description be construed as encompassing all of the features of patentable novelty that reside in the present invention, including all the features and embodiments that would be treated as equivalents thereof by those skilled in the relevant art. Thus, it is intended that the scope of the present invention herein disclosed should not be limited by the particular disclosed embodiments described above but should be determined only by a fair reading of complete specification to follow.

[0183] 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.

[0184] Reaction scheme:

[0185] B-1 B-2 B-3 B-4

[0186]

[0187] (S)-(+)-Fluxamitamide

[0188] C20H16CI2F3N3O3

[0189] Mol. Wt.: 474.26

[0190] Example 1: Preparation of 2,2,2-Trifluoro-l-(3-nitro-phenyl)-ethanone (A-2)

[0191] (CF3CO)2O &

[0192] A-1 A-2 Method A:

[0193] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, was charged with EDC (750 mL) followed by nitrobenzene (214.3 g). Catalyst ZSM-5 (10.5 g) was added. Trifluoroacetic anhydride (TFA) (421.3 g) was added dropwise over 30 mins and then the reaction mass refluxed for 8 hrs. After completion of the reaction, the reaction mass was filtered and the filtrate was poured slowly over saturated sodium bicarbonate solution and stirred for 30 mins. The organic layer was separated. Aqueous layer was washed with EDC (150 mL). The combined organic layer washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish 2,2,2-Trifluoro-l-(3- nitro-phenyl)-ethanone (A-2). After purification, HPLC purity (area): 95%, Yield: 287.8 g, 77 %. Method B:

[0194] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, was charged with EDC (700 mL) followed by nitrobenzene (183.7 g). Catalyst ZSM-5 (9 g) was added. Trifluoroacetic acid (425.3 g) was added dropwise over 45 mins and then the reaction mass refluxed for 17 hrs. After completion of the reaction, the reaction mass filtered and the filtrate was poured slowly over saturated sodium bicarbonate solution and stirred for 30 mins. The organic layer was separated. Aqueous layer was washed with EDC (150 mL). The combined organic layer washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish 2,2,2-Trifluoro-l-(3-nitro-phenyl)- ethanone (A-2). After purification, HPLC purity (area): 95%, Yield: 205 g, 64 %.

[0195] Example 2: Preparation of l-(3-Chloro-5-nitro-phenyl)-2,2,2-trifluoro-ethanone (A-3)

[0196] A-2 A-3

[0197] A pressure reactor was charged with acetic acid (250 mL) followed by 2,2,2-Trifluoro-l-(3- nitro-phenyl)-ethanone (184.2 g). Anhydrous ferric chloride (3.4 g) was added. The reactor was filled with chlorine gas and the pressure of chlorine gas was held at 6 Bar. The reaction was heated to 120° C for 16 hrs under constant stirring. After completion of the reaction, the excess chlorine gas was quenched. Ethylene dichloride (500 mL) was added to the reaction mass and it was poured slowly over aqueous sodium hydroxide and stirred for 30 mins. The organic layer was separated. Aqueous layer was washed with EDC (100 mL). The combined organic layer washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish l-(3-Chloro-5-nitro-phenyl)-2,2,2-trifluoro-ethanone (A-3). After purification, HPLC purity (area): 95%, Yield: 127.6 g, 63 %.

[0198] Example 3: Preparation of l-(3,4-Dimethyl-phenyl)-ethanone (B-2)

[0199] B-1 B-2 A four necked glass reactor (5 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, calcium chloride guard tube was charged with EDC (2500 mL) followed by o-Xylene (526.3 g) and Aluminum chloride (512.7 g). The mixture was cooled to 10° C. Acetyl chloride (320.7 g) was added dropwise over 45 mins under vigorous stirring. After complete addition of acetyl chloride, the reaction mass was allowed to warm to room temperature and stirred for 3.5 hrs. After completion of the reaction, the reaction mass was slowly poured over ice-cold 10% HC1. After complete quenching, the mass was brought to room temperature. Organic layer was separated. The aqueous layer was washed with EDC (350 mL). The combined organic layer washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to furnish) l-(3,4-Dimethyl-phenyl)-ethanone (B-2). After purification, HPLC purity (area): 92%, Yield: 530.48 g, 76 %.

[0200] Example 4: Preparation of Methyl 4-Acetyl-2-methyl-benzoate (B-3)

[0201] 1. MEG, p-TSA

[0202] B-2 B-3

[0203] A four necked glass reactor (3 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, calcium chloride guard tube was charged with EDC (750 mL) followed by l-(3,4-Dimethyl-phenyl)-ethanone (B-2) (206.5 g), Monoethylene glycol (MEG) (419 g), and p-Toluenesulfonic acid (p-TSA) (4.6 g). The reaction mass was heated to 70-75° C for 7 hrs. After completion of the reaction, the reaction mass was cooled to room temperature, quenched with addition of water (500 mL). The organic layer was separated and washed with brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish 2-(3,4-Dimethyl-phenyl)-2-methyl-[l,3]dioxolane (ketal derivative of B-2). The weight of crude material: 202.1 g. The crude material was used without further purification for the next conversion.

[0204] A pressure reactor (2 lit) was charged with acetic acid (300 mL) followed by 2-(3,4-Dimethyl- phenyl)-2-methyl-[l,3]dioxolane (200 g) followed by Cobalt (II) acetylacetone [(Co(acac)2] (2.9 g), Tetra-n-butyl ammonium bromide (TBAB) (6.9 g). The pressure reactor was closed. The stirring was started. The reactor was flushed twice with oxygen. The reactor was filled with oxygen and pressure was taken to 5 bar. The reactor was heated to 110-115° C. After attaining the temperature, oxygen pressure was elevated to 10 Bar. The reaction was continued for 9 hrs till completion. After completion of the reaction, the reactor was cooled down to room temperature, excess oxygen was bubbled through water before opening of the reactor. Acetic acid was distilled out and the residue was poured on ice-cold NaOH solution (5M). The aqueous layer washed with EDC (200 mL). The aqueous layer was acidified with concentrated HC1 at lower temperature. The solid obtained was filtered and dried till constant weight to furnish 4-Acetyl-2-methyl-benzoic acid. HPLC purity (area): 98%, Yield: 154.7 g, 69 %.

[0205] A four necked glass reactor (5 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube was charged with 4-Acetyl-2-methyl-benzoic acid (300 g) dissolved in Methanol (750 mL), followed by AA-Dimethylformamide (DMF) (1.4 g) at room temperature. Thionyl chloride (342.6 g) was added dropwise over 45-50 mins under vigorous stirring at 0° c to 5° C. After complete addition of thionyl chloride, the reaction mass was warmed to room temperature and then refluxed briefly to ensure complete conversion of acid to the ester. The reaction mass was cooled to rt and methanol was removed under vacuum. The residue was diluted with EDC (750 mL). Water (350 mL) was added. The Organic layer was separated. Aqueous layer was washed with EDC (200 mL). The combined organic layer was washed with brine (500 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to furnish Methyl 4-Acetyl-2-methyl-benzoate (B-3). After purification, HPLC purity: 97%, Yield: 209.6 g, 85 %.

[0206] Example 5: Preparation of Methyl 4-(2-Bromo-acetyl)-2-methylbenzoate (B-4)

[0207] B-3 B-4

[0208] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Calcium chloride guard tube was charged with Methyl 4-Acetyl-2-methyl- benzoate (189.5 g) dissolved in EDC (550 mL) followed by AIBN (6.4 g). A-Bromo succinimide (NBS) (189 g) 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 (150 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 Methyl 4-(2-Bromo-acetyl)-2- methylbenzoate (B-4). After purification, HPLC purity: 95%, yield: 193 g, 76%.

[0209] Example 6: Preparation of Methyl 4-[3-(3-Chloro-5-nitro-phenyl)-4,4,4-trifluoro-but-2- enoyl]-2-methylbenzoate (C-l)

[0210] Wittig Horner

[0211] A-3 B-4

[0212] A three necked glass reactor (2 Lit) fitted with thermometer pocket, thermometer, mechanical stirrer was charged with dry Toluene (150 mL) followed by triphenylphosphine (184.7 g) under nitrogen atmosphere. Methyl 4-(2-Bromo-acetyl)-2-methylbenzoate (144.3 g) dissolved in dry Tetrahydrofuran (THF) (300 mL) was added in single lot at room temperature. Sodium methoxide powder (38 g) 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-Chloro-5- nitro-phenyl)-2,2,2-trifluoro-ethanone (152.7 g) dissolved in dry Toluene (450 mL). The gradual decolorization of the reaction was seen indicating the reaction progress. After stirring for 2 hr, the reaction was slowly poured on cooled 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 Methyl 4-[3-(3-Chloro-5-nitro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methylbenzoate (C-l). After purification, HPLC purity: 97%, yield: 188.3 g, 80%.

[0213] Example 7: Preparation of 4-[5-(3-Chloro-5-nitro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (C-2) A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, was charged with aqueous solution of hydroxylamine hydrochloride (28.5 g in 40 mL water) followed by aqueous sodium hydroxide (17.9 g in 40 mL water). This mixture is cooled to 5 to 10° C. Intermediate (C-l) (160.8 g) dissolved in MeOH (500 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 HC1 (110.9 g, 30%) was added slowly. 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 -Chloro-5-nitro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3 -yl] -2-methyl- benzoic acid methyl ester (C-2) as solid. The solid material was filtered, dried and recrystallized form IPA. After purification, HPLC purity: 96%, yield: 121.1 g, 75%.

[0214] Example 8: Preparation of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzoic acid (C-3)

[0215] 1 Reduction CI

[0216] Step 1: In an autoclave reactor (2 Lit), 4-[5-(3-Chloro-5-nitro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (C-2) (114.6 g) was charged followed by Methanol (400 mL). 5% Pd / C (1.5 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. 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 4-[5-(3-Amino-5-chloro-phenyl)-5-trifluoromethyl- 4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester. Crude weight: 86.2 g. This crude material was used for the next step. Step 2: In a four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, Sodium nitrite (15.6 g) dissolved in water was added dropwise to Cone. Sulfuric acid (100.6 g) without allowing the reaction mass temperature to rise above 5° C. To this nitrous acid solution, 4-[5-(3-Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (85 g) dissolved in Acetic acid (180 mL) was added dropwise over 1.5 hr at 0°C to 5° C. After completion of the addition, the reaction was maintained at the same temperature for 30 mins. Cuprous chloride (24.6 g) was added in lots at the same temperature. After addition of Cuprous chloride, 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 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl- benzoic acid methyl ester. After purification, HPLC purity: 95%, yield: 66.1 g, 76%.

[0217] Step 3:

[0218] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, was charged with Methanol (400 mL) followed by 4-[5-(3,5-Dichloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (200 g). This was stirred for to make homogenous solution. To this solution, sodium hydroxide (42 g dissolved in 150 mL water) was added in a single lot. The reaction was stirred at room temperature for 6-7 hrs to get a clear solution. The reaction was monitored by HPLC. After 6- 7 hrs, the reaction was complete and the reaction mass was cooled to room temperature. The reaction mass was acidified till pH 6 by using HC1 to obtain solid. The solid thus obtained was filtered, dried till constant weight. HPLC purity: 97%, yield: 163.6 g, 89%.

[0219] Example 9: Preparation of S-(+)- 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid, S-(+)-(C-4) by resolution

[0220] A three necked RB flask (1 lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer, was charged with 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzoic acid (68.4 g) dissolved in Tetrahydrofuran (THF) (350 mL). (S)-(-)-a-Methylbenzylamine (19.22 g) dissolved in THF (100 mL) was added dropwise. The diastereomeric salt as solid separated out. The mixture was briefly heated for 30 mins and filtered. The solid residue was washed with THF (2 X 25 mL). The solid material was recrystallized from ethanol. Weight of the recrystallized diastereomeric salt (S, S): 39.4 g. This diastereomeric salt was neutralized with 1.5 N HC1 to give the desired enantiomer. Weight of the product: 27.63 g. The chiral purity of the enantiomer was determined using Thermo Fisher HPLC (Vanquish) with a DAD detector, (Wavelength: 254 nm) by Hypersil Chiral -OT Column (250 mm length X 4.6 mm I.D., 5 pm particle size) at room temperature. Mobile phase of MeOH / Formic Acid (100:0.100, v / v) was pumped at flow rate of 1.0 mL / min.

[0221] Retention time of (S)-(C-4) acid: 4.38 min, chiral purity: 97.6 %.

[0222] The above filtrate was concentrated to furnish the another diastereomeric salt (S,R). After recrystallization, the salt was neutralized with 1.5 N HC1 to give (R)-(C-4) acid.

[0223] Retention time of (R)-(C-4) acid: 3.84 min, chiral purity: 91.7 %

[0224] Example 10: Preparation of (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5- dihydro-isoxazol-3-yl]-2-methyl-benzamide, (C-5) -

[0225] A three necked RB flask (0.5 Lit) fitted with thermometer pocket, thermometer, mechanical stirrer, anhydrous calcium chloride guard tube was charged a solution of S-(+)- 4-[5-(3,5- Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid in EDC (120 mL). VA-Dimcthylformamidc (0.4 g) was added as a catalyst. Thionyl chloride (12.5 g) was added drop wise. After complete addition, the reaction mass was refluxed briefly to ensure complete reaction. After completion of the reaction, the reaction mass was cooled to +10- 15° C and aqueous ammonia (14 g) was added dropwise. The reaction mass then stirred at room temperature for 3-4 hrs. The reaction mass was diluted with EDC (200 mL). The organic layer was separated and washed successively with water, brine, dried over anhydrous sodium sulfate and filtered. The organic layer was concentrated to furnish (S)-4-[5-(3,5-Dichloro-phenyl)-5- trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide, (C-5). After purification, HPLC purity: 97%, yield: 34.2 g , 95%

[0226] Example 11: Preparation of (S)-(+)-Fluxametamide

[0227] (S)-(+)-Fluxamitamide

[0228] A three necked RB flask (0.5 L) fitted with thermometer pocket, thermometer, mechanical stirrer, anhydrous calcium chloride guard tube was charged A,A-Dimethyl formamide (DMF) (80 mL). The RB flask was ice cooled and Phosphorous oxychloride (15.6 g) was added dropwise. An exothermic reaction occurred with the formation of the phosphorus oxychloridedimethylformamide complex. After complete addition of POCI3, the reaction mass was stirred for 15 mins in ice bath followed by addition of (S)-4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzamide (33.7 g) dissolved in DMF. The reaction was allowed to warm to room temperature and then heated at 75-80° C. 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 the N-Formyl-4-[5-(3,5- dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (34.12 g)-

[0229] The residue was dissolved in methanol (100 mL) and cooled in ice bath. Methoxylamine hydrochloride (5.4 g) was added as a solid. To this mixture, sodium hydroxide (2.5 g) in water (10 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 (S)-(+)-Fluxametamide. The product was crystallized from 2-propanol twice. After purification, HPLC purity: 98.4 %, Chiral purity; 98.4 %, RT: 8.46 min, yield: 22.4 g, 87 %

[0230] The present invention is more specifically explained by examples given above.

[0231] 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

I / WE CLAIM:Claim 1: A process for the preparation of optically pure Fluxametamide of Formula (I), wherein, the said process comprises the steps of: i. coupling l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A-3), with methyl 4-(2-bromoacetyl)-2-methylbenzoate (compound B-4), to obtain methyl 4- [(2Z)-3-(3-chloro-5-nitrophenyl)-4,4,4-trifluorobut-2-enoyl]-2-methylbenzoate (intermediate C-l); ii. cyclizing the intermediate (C-l), in the presence of hydroxylamine hydrochloride followed by acid mediated ring closure using a suitable solvent to yield methyl 4-[5-(3- chloro-5-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2-oxazol-3-yl]-2- methylbenzoate (dihydroisoxazole compound (C-2)); iii. hydrogenating the dihydroisoxazole compound (C-2), in the presence of hydrogen and suitable catalysts, or by transfer hydrogenation at atmospheric pressure or up to 50 Bar pressure using suitable solvent to yield a corresponding aniline, (Methyl 4-[5-(3- Amino-5-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl- benzoate) followed by diazotization and treatment with cuprous chloride (CuCl) and hydrolysis to obtain 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-l,2- oxazol-3-yl]-2-methylbenzoic acid (compound C-3), wherein the compound C-3 is a racemic compound; iv. resolving the racemic compound (C-3) in the presence of resolving agent(s) selected from chiral amines or chiral alcohols, to obtain a diastereomeric salt or diastereomeric ester; v. recrystallizing the diastereomeric salt or ester obtained in step (iv) from the suitable solvent, followed by release of free acid by treatment of the diastereomeric salt or ester with acid to obtain an enantiomer of the acid (compound C-4); vi. converting the enantiomer of the acid (compound C-4) obtained in step (v), to a corresponding benzamide 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-benzamide, followed by formylation using phosphorous oxychloride and N, A- Di methyl formamide (DMF) to obtain (compound C-5); vii. treating the compound C-5; with methoxyamine hydrochloride to obtain a chirally pure Fluxametamide of formula (I).Claim 2: An alternative process of obtaining the enantiomer of the acid (C-4) as claimed in claim 1, which comprising treating the compound (C-3) with the suitable chiral alcohol in the presence of acid to obtain a diastereomeric ester, which is further hydrolyzed to obtain the enantiomer of the acid (C-4).Claim 3: A process for the preparation of the compound (A-3), comprising: i. subjecting nitrobenzene (A-l) to acylation in the presence of acylating agent and Lewis acids to obtain 2,2,2-trifluoro-l-(3-nitrophenyl)ethan-l-one (compound A-2); ii. halogenating the compound (A-2) as obtained in step (i) in the presence of halogenating agent to obtain l-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-l-one (compound A-3).Claim 4: A process for the preparation of methyl 4-(2-bromoacetyl)-2-methylbenzoate (compound B-4), comprising: i. subjecting a compound (o-Xylene) (B-l) to acylation in the presence of an acylating agent and Lewis acids to obtain l-(3,4-dimethylphenyl)ethan-l-one (compound B-2); ii. protecting the compound (B-2) as ketal derivative ( / '.<?., 2-(3,4-Dimethyl-phenyl)-2- methyl-[l,3] dioxolane), followed by oxidation under controlled conditions to obtain a corresponding acid, i.e., 4-Acetyl-2-methyl-benzoic acid ; iii. converting the corresponding acid obtained in step (ii) to acid chloride, 4-Acetyl-2- methylbenzoyl chloride in the presence of halogenating agents followed by treatment with suitable alcohol, to furnish methyl 4-acetyl-2-methylbenzoate (compound B-3); iv. subjecting the compound (B-3) obtained in step (iii) to halogenation in the presence of halogenating agent and suitable solvent to provide a compound (B-4), i.e., methyl 4-(2- bromoacety 1) -2 -methylbenzoate .Claim 5: The process as claimed in claims 1-4, wherein the acylating agent is selected from the group comprises of Trifluoroacetyl chloride or trifluoroacetic anhydride or trifluoroacetic acid, acetyl chloride, acetic anhydride or combination thereof.Claim 6: The process as claimed in claims 1-4, wherein the Lewis acid is selected from the group comprises of Zinc chloride (ZnCh), Aluminium Chloride (A1CL), Ferric Chloride (FeCL), Boron Trifluoride (BF3), Boron Trichloride (BCI3), Titanium tetrachloride (TiCL), Antimony Pentafluoride (SbFs), Thionyl chloride (SOCI2), Copper Chloride (CuCh), mineral acids such as hydrochloric acid, Sulfuric acid (H2SO4), Nitric acid (HNO3), etc., any metaltriflates or Zeolites or combination thereof.Claim 7: The process as claimed in claims 1-4, wherein the halogenating agent is selected from a chlorinating agent or a brominating agent or combinations thereof.Claim 8: The process as claimed in claim 7, wherein the chlorinating agent is selected from the group comprising Chlorine gas or Chlorine in acetic acid or A-Chlorosuccinimide, Thionyl chloride, Oxalyl chloride, Phosphorous trichloride or phosphorous pentachloride in Methyl alcohol or combination thereof.Claim 9: The process as claimed in claim 7, wherein the brominating agent is selected from the group comprising aqueous HBr & H2O2, KBr, H2O2 & H2SO4 or A-bromosuccinimide (NBS) or combination thereof.Claim 10: The process as claimed in claims 1-4, wherein the halogenating agent is further selected from the group comprising Chlorine gas or Chlorine in acetic acid or N- Chlorosuccinimide, Thionyl chloride, Phosphorous trichloride or phosphorous pentachloride, HBr & H2O2, KBr, H2O2 and H2SO4 or N-bromosuccinimide (NBS) or combination thereof.Claim 11: The process as claimed in claims 1-4, wherein the suitable solvent is selected from the group comprises of Ethylene chloride, Ethylene dichloride (EDC), Methylene dichloride (MDC), Chlorobenzene, methanol, ethanol, 2-propanol, tert-butyl alcohol, n-butyl alcohol, sec-butyl alcohol, ethyl acetate, acetic acid, N,N-dimethylformamide (DMF), benzene, chloroform, 1, 4-dioxane, diethyl ether, acetic acid, o-dichlorobenzene, carbon tetrachloride, chlorobenzene, dichlorobenzene, tetrahydrofuran and acetonitrile, Acetone, dimethylsulfoxide, cyclohexane, hexane, heptane, toluene, xylene, Isopropanol / 2 -propanol, water, brine, sodium sulphate or water combination thereof.Claim 12: The process as claimed in claims 1-4, wherein the formylating agent is selected from the group comprises of para-formaldehyde, formalin, formic acid, methyl formate, N,N- dimethylformamide, diazomethane, cyanogen bromide, or combination thereof in the presence of other reagents such as phosphorous oxychloride.Claim 13: The process as claimed in claims 1-4, wherein the suitable catalyst is selected fromthe group comprises of 5-10% Pd on Charcoal or 5% Pt on Charcoal or Raney-Nickel, ZSM- 5, radical initiators including Azobisisobutyronitrile (AIBN), Benzoyl peroxide, ZSM-5, Cobalt (II) acetylacetone [(Co(acac)2], Tetra-n-butyl ammonium bromide (TBAB), and , phase transfer catalysts like quaternary ammonium or phosphonium salts or combination thereof.Claim 14: The process as claimed in claims 1-4, wherein the acid is selected from the group comprising of organic or inorganic acid or combination thereof.Claim 15: The process as claimed in claim 14, wherein the organic or inorganic acid is selected from the group comprising of hydrochloric acid (HC1), Sulfuric acid (H2SO4), Nitric acid (HNO3), phosphoric acid, orthophosphoric acid, acetic acid, propanoic acid, p-Toluene sulfonic acid (p-TSA), benzene sulfonic acid, methane sulfonic acid or combination thereof.Claim 16: The process as claimed in claims 1-4, wherein the chiral amine is selected from the group comprises of (R)-(+)-a-Methylbenzylamine, (S)-(-)-a-Methylbenzylamine, (S)-(+)-l- Cyclohexylethylamine, (R)-(+)-a,4-Dimethylbenzylamine, (R)-(+)-a-Ethylbenzylamine, (S)- (-)-a-Ethylbenzylamine (R)-4-Fluoro-a-methylbenzylamine or combination thereof.Claim 17: The process as claimed in claims 1-4, wherein the chiral alcohol is selected from the group comprises of (S)-(+)-2-Butanol, (R)-(-)-2-Butanol, (S)-(-)-2-Methyl-l-butanol, (S)-(+)- 2-Octanol, (R)-(-)-2-Octanol, (R)-(+)-l -Phenylethylalcohol, (S)-(-)-l-Phenylethylalcohol, (R)-(-)-l-Phenyl-2,2,2-trifluoroethanol, (S)-(+)-l-Phenyl-2,2,2-trifluoroethanol or combination thereof.Claim 18: The process as claimed in claim 4, wherein the suitable alcohol is selected from methyl alcohol (methanol), ethanol, 2-propanol, tert-butyl alcohol, n- butyl alcohol, .vec-butyl alcohol or combination thereof.Claim 19: A process for preparing agrochemical composition comprising optically pure Fluxametamide of Formula (I) as obtained by the process claimed in claims 1-18.Claim 20: An agrochemical composition, wherein the composition comprises at least a bioactive effective amount of optically pure Fluxametamide of Formula (I) as obtained by the process claimed in claims 1-18.Claim 21: The agrochemical composition as claimed in claim 20, which further comprises one of more agrochemically acceptable excipients.Claim 22: A process for preparing the agrochemical composition comprising optically pure Fluxametamide of Formula (I) as claimed in claims 20-21.

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