A method for the preparation of substituted 1-(4-(5-(halomethyl)-1,2,4-oxadiazol-3-yl)phenyl)ethan-1-one

Abstract

A method for the preparation of substituted 1-(4-(5-(halomethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one The present invention relates to a method for preparing a compound of Formula (I) and its intermediate compound of Formula (II) and their N-oxides or agriculturally acceptable salts thereof, wherein R1, R2, L, R4 and n are as defined in the description. The present method comprises a novel and inventive step of converting a dioxime compound of Formula (II) to a compound of Formula (I) in a single step via a simultaneous cyclization and deprotection of the dioxime compound to obtain the compound of Formula (I).

Description

[0001]PI External Title: A method for the preparation of substituted 1-(4-(5-(halomethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one Field of the Invention The present invention relates to a method for the preparation of substituted 1-(4-(5-(halomethyl)-1,2,4- 5 oxadiazol-3-yl)phenyl)ethan-1-one of Formula (I), an intermediate compound of Formula (II) and N- oxides or agriculturally acceptable salts thereof, useful for combating phytopathogenic fungi. wherein R1, L, R2and n are as defined in the description. Background and Prior art of the Invention 10 Oxadiazole based compounds are well known for their pesticidal activity. Various oxadiazoles have been disclosed in the literature. For example, WO2017118689 discloses a microbiocidal oxadiazole compound of Formula (I), 15 was as an WO2020208511 discloses the preparation of oxadiazole compounds bearing a carbonyl group, which includes protection of the carbonyl group of the nitrile reactant with ethylene glycol, followed by a reaction with aqueous hydroxylamine, furthermore by a cyclization with trifluoroacetic anhydride, and finally deprotection of the cyclic ether to obtain the oxadiazole compounds bearing a carbonyl group. 20 The disclosed process is lengthy, involves too many reagents and purification steps at every stage, and is eventually less atom economic. PI External Hence, there is a need for a method for preparing such compounds which is short, high yielding and more atom economic, wherein both cyclization to oxadiazole, and deprotection of ketoxime takes place simultaneously in a single step. Objective of the Invention 5 The objective of the present invention is to provide a novel, more economic and improved method for preparing the compound of Formula (I) and the intermediate compound of Formula (II) and their N- oxides or agriculturally acceptable salts thereof, in a reduced number of steps and with high isolated yield, suitable for a commercial scale preparation. The present invention provides a solution to this objective by offering a simple, and economically 10 amenable method for obtaining a compound of Formula (I), its N-oxides or agriculturally acceptable salts thereof, in high yields and a reduced number of reaction steps, wherein the method comprises a novel and inventive step of simultaneous cyclization and deprotection of a compound of Formula (II) in a single step, by overcoming at least one of the shortcomings disclosed in the prior art. 15 Summary of the Invention Accordingly, the first aspect of the present invention provides a method for preparing a dioxime compound of Formula (II) or its N-oxide or an agriculturally acceptable salt thereof, wherein, 20 L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, 25 wherein said method comprising the steps of: PI External a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V), ; b. reacting the compound of Formula (V) with a compound of Formula (IV) and a base in a 5 solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), ; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain a dioxime compound of Formula (II), . 10 In a second aspect, the present invention provides a method for preparing a compound (substituted 1- (4-(5-(halomethyl)-1,2,4-oxadiazol-3-yl)phenyl)ethan-1-one) of Formula (I), or its N-oxides or agriculturally acceptable salts thereof, 15 wherein, R1is selected from -CHF2, -CF2-Cl or CF3; L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; 20 R3is selected from hydrogen or C1-C6-alkyl; and PI External n is an integer selected from 1-2, wherein said method comprising the steps of: a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V), 5 ; b. reacting a compound of Formula (IV) with the compound of Formula (V) and a base in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), ; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally 10 in the presence of a base, to form a dioxime compound of Formula (II), ; and d. cyclizing the dioxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step, 15 , wherein R4is selected from halogen, OH, C1-C6-alkoxy or O-C(O)-R1. In a third aspect, the present invention provides a method for the synthesis of compounds of Formula (VI) or agriculturally acceptable salts thereof, comprising the steps of: PI External i. acetylating a compound of Formula (IX) with acetyl chloride or acetic anhydride in the presence of a suitable catalyst and a solvent to obtain a compound of Formula (VIII), ; and ii. reacting the compound of Formula (VIII) with a cyanide source in a solvent, optionally in the 5 presence of a catalyst, to obtain a compound of Formula (VI), . In yet another aspect, the present invention further relates to a method for preparing a compound of Formula (I), or its N-oxides or agriculturally acceptable salts thereof, wherein said method comprises the step (step-d) of cyclizing a dioxime compound of Formula (II) by reacting it with a compound of 10 Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step, , wherein R4is selected from halogen, C1-C6-alkoxy, OH or O-C(O)-R1and R1, R2, L and n are as described above. 15 In yet another aspect, the present invention provides a method for preparing a compound of Formula (II) or its N-oxides or an agriculturally acceptable salt thereof, wherein, PI External L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and 5 n is an integer selected from 1-2, wherein said method comprising the step of: reacting a compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain a dioxime compound of Formula (II) (step-c), 10 R2, L and n are as described above. DETAILED DESCRIPTION OF THE INVENTION As used herein, the terms “comprises”, “comprising”, “includes”, “including”, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, process or method that comprises a list of elements is not necessarily limited to only those 15 elements but may include other elements not expressly listed or inherent to process or method. Also, the indefinite articles “a” and “an” preceding an element or component of the present invention are intended to be non-restrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore “a” or “an” should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be 20 singular. The compounds of the present disclosure may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers. The various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within 25 the scope of the claims of the present disclosure. One skilled in the art will appreciate that one stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additionally, the person skilled in the art knows processes or methods or technology to separate, enrich, and / or to selectively prepare said isomers. PI External The compounds of the present disclosure may be present in the form of N-oxides or salts. The compounds of the present invention may be an acid addition or base addition salt. The acid addition salt includes inorganic or organic acid preferably hydrochloric acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid. The base addition salt includes inorganic or organic base preferably alkali 5 metal salt or alkaline earth metal salt. Unless otherwise specifically mentioned, the term “halogen” used in the present invention refers to fluoro, chloro, bromo or iodo. The term “C1-C6alkyl” used in the present invention refers to a linear or branched alkyl with 1 to 6 carbon atoms. Examples of C1-C6includes but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, 10 isobutyl, sec-butyl, t-butyl, n-pentyl or n-hexyl and the like. The term “C1-C6 haloalkyl” used in the present invention refers to a linear or a branched alkyl with 1 to 6 carbon atoms, which is substituted with one or more halogen. Examples includes but not limited to chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, difluoromethyl, trifluoroethyl, perfluoroethyl and the like. 15 The term “C1-C6 alkoxy” used in the present invention refers to a linear or a branched alkoxy with 1 to 6 carbon atoms. Examples includes but not limited to methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, t-butoxy and the like. The term “C3-C6 cycloalkyl” used in the present invention refers to a 3- to 6-membered saturated monocyclic carbocyclic ring. Examples includes but not limited to cyclopropyl, cyclobutyl, cyclopentyl 20 and the like. In the context of the present invention, the term “optionally” when used in reference to any element, to intermediates, reagents or conditions, including any method step, e.g., the isolation of intermediates; is intended to mean that the subject element is isolated, or alternatively is not isolated from the reaction mixture and directly used for the subsequent chemical reaction. Similarly, this definition is applied in 25 case for reagents or reaction conditions as well. The specification herein and the various features and advantageous details thereof are explained with reference to the non-limiting examples in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the 30 specification herein may be practiced and to further enable those of skilled in the art to practice the specification herein. Accordingly, the examples should not be construed as limiting the scope of the specification herein. PI External The description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning 5 and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein. 10 Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application. 15 It is well recognized that preparing a compound bearing a carbonyl moiety from a starting material containing a reactive carbonyl group, is tedious and may often lead to unwanted side products due to competitive reactions among the reaction site and the reactive carbonyl group. Hence, such processes always require specific protection and de-protection of the reactive carbonyl group to eliminate such competitive reactions to minimise the side product formation. Therefore, there is a need for the 20 development of a method for preparing the compound of Formula (I), which does not require any specific protection and de-protection steps of the carbonyl group while not compromising on the yield of the final product. Embodiment-001: The present invention provides a method for preparing a compound of Formula (II) or its N-oxides or an agriculturally acceptable salts thereof, 25 wherein, L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; 30 R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, PI External wherein said method comprising the steps of: a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V), ; 5 b. reacting a compound of Formula (IV) with the compound of Formula (V) and a base in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain a dioxime compound of Formula (II), 10 . Embodiment-002: The present invention also provides a method for preparing a compound of Formula (I), or its N-oxides or agriculturally acceptable salts thereof, wherein, 15 R1is selected from -CHF2, -CF2-Cl or CF3; L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and PI External n is an integer selected from 1-2, wherein said method comprising the steps of: a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V), 5 ; b. reacting the compound of Formula (V) with a compound of Formula (IV) and a base in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), ; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally 10 in the presence of a base, to form a dioxime compound of Formula (II), d. cyclizing the dioxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step, 15 , wherein, R4is selected from halogen, OH, C1-C6-alkoxy or O-C(O)-R1. Embodiment-003: The present invention further provides a method for the synthesis of compounds of Formula (VI) or their agriculturally acceptable salts thereof, comprising the steps of: i. acetylating a compound of Formula (IX) with acetyl chloride or acetic anhydride in the presence 20 of a suitable catalyst and a solvent to obtain a compound of Formula (VIII), PI External ; and ii. reacting the compound of Formula (VIII) with a cyanide source in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (VI), , 5 wherein X is as defined above. Embodiment-004: The present invention still further relates to a method for preparing a compound of Formula (I), or its N-oxides or agriculturally acceptable salts thereof, , wherein, 10 R1is selected from -CHF2, -CF2-Cl or CF3; L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and 15 n is an integer selected from 1-2, wherein said method comprises the step (step-d) of cyclizing a dioxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step, , 20 wherein R4is selected from halogen, C1-C6-alkoxy, OH or O-C(O)-R1and PI External R1, R2, L and n are as described above. Embodiment-005: The present invention still further provides a method for the synthesis of a compound of Formula (II) or its N-oxides or agriculturally acceptable salts thereof, comprising the steps of: 5 A. preparing a compound of formula (VI) by acetylating a compound of Formula (IX) with acetyl chloride or acetic anhydride in the presence of a suitable catalyst and a solvent to obtain a compound of Formula (VIII), ; ii. reacting the compound of Formula (VIII) with a cyanide source in a solvent, optionally in the 10 presence of a catalyst, to obtain a compound of Formula (VI), ; halogenating the compound of Formula (VI) obtained by step (A) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V), ; 15 reacting the compound of Formula (V) with a compound of Formula (IV) and a base in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), ; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (II), PI External . Embodiment-006: The present invention still further provides a method for the synthesis of compounds of Formula (I) or their N-oxides or agriculturally acceptable salts thereof, comprising the steps of: 5 A. preparing a compound of formula (VI) by i. acetylating a compound of Formula (IX) with acetyl chloride or acetic anhydride in the presence of a suitable catalyst and a solvent to obtain a compound of Formula (VIII), ; ii. reacting the compound of Formula (VIII) with a cyanide source in a solvent, optionally in the 10 presence of a catalyst, to obtain a compound of Formula (VI), ; a. halogenating the compound of formula (VI) obtained by step (A) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of formula (V), ; 15 b. reacting the compound of Formula (V) with a compound of Formula (IV) and a base in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III), PI External ; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (II), 5 d. cyclizing the dioxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step, , wherein R4is selected from halogen, C1-C6-alkoxy, OH or O-C(O)-R1. 10 Embodiment-007: The method(s) of the present invention according to any of the embodiments 002, 004 and 006 for preparing the compound of Formula (I), or its agriculturally acceptable salts or N- oxides as described above, involves a novel and inventive step, wherein the dioxime intermediate compound of Formula (II) undergoes a simultaneous cyclization of N-hydroxyimidamide moiety and deprotection of ketoxime, to obtain the compounds of Formula (I) in a single step. 15 Embodiment-008: The methods of the present invention according to any of the embodiments 002, 004 and 006 for preparing the compound of Formula (I), or its agriculturally acceptable salts or N- oxides as described above, can be obtained in fewer reaction steps by eliminating the reaction steps required for the separate protection and deprotection of the carbonyl group of the intermediates to obtain the final product. As a consequence, the present method(s) eliminate(s) the use of additional reactants, 20 reagents and solvents required for performing said conversions and also, eventually avoid(s) the isolation or purification steps of the compounds formed during said conversions. Altogether, it enables the method(s) of the present invention for obtaining the compound of Formula (I), in a simple, short, environmentally friendly and commercially viable method over the methods already known in the prior art. PI External Embodiment-009: Further, the method(s) of the present invention is more atom economic and provides the product and the key intermediates in high isolated yields. Embodiment-010: The methods of the present invention according to any of the embodiments 002, 004 and 006, wherein, if ethyl trifluoracetate (R1= CF3and R4is OEt or OMe or Cl or O-C(O)CF35 in Formula (VII)) is used for the cyclization purpose to obtain the oxadiazole ring, then ethyl trifluoroacetate or its trans-esterified product i.e., methyl trifluoroacetate obtained as a side-product, can be recovered and re-used for the cyclization step and as a result, the present methods are significantly economic for commercial scale preparation, and it also reduces the quantity of effluent generated during the process to minimize the environmental pollution. 10 Embodiment-011: The methods of the present invention according to any of the embodiments 002, 004 and 006, wherein for the compound of Formula (I), R1may be selected from CF3 or CF2Cl, preferably CF3; L may be selected from O, NH or S; R2may be selected from hydrogen, halogen, C1- C3 alkyl or C1-C3 alkoxy; and n is 1-2. Embodiment-012: The methods of the present invention according to embodiment-011, wherein 15 R1is preferably selected from CF3; L is preferably selected from O, NH or S; R2is preferably selected from hydrogen, fluoro, chloro, bromo, methyl or methoxy; and n is 1-2, particularly n = 1. Embodiment-013: The methods of the present invention according to embodiment-012 wherein R1is CF3, L is O and n = 1-2, R2is preferably selected from fluoro (F), chloro (Cl), bromo (Br), methyl (Me) or methoxy (OMe); preferably 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4- 20 Me, 2-Me, 3- OMe, 4-OMe, 2,4-di-fluoro, or 3,4-di-fluoro. Embodiment-014: The methods of the present invention according to embodiment-012, wherein R1is CF3, L is NH and n = 1-2, R2is preferably selected from fluoro, chloro, bromo, methyl or methoxy; preferably 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4-Me, 2-Me, 3-OMe, 4-OMe, 2,4-di-fluoro, or 3,4-di-fluoro. 25 Embodiment-015: The methods of the present invention according to embodiment-012, wherein R1is CF3, L is S and n = 1-2, R2is preferably selected from fluoro, chloro, bromo, methyl or methoxy; preferably 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4-Me, 2-Me, 3-OMe, 4- OMe(methoxy), 2,4-di-fluoro, or 3,4-di-fluoro. Embodiment-016: The methods of the present invention according to any of the embodiments- 30 001, 002, 004, 005 and 006, wherein for the compound of Formula (II), Formula (III) and Formula (IV), L may be selected from O, NH or S; R2may be selected from hydrogen, halogen, C1-C3alkyl or C1-C3alkoxy; and n is 1-2. Embodiment-017: The methods of the present invention according to embodiment-016, wherein L is selected from O, NH or S; R2is preferably selected from hydrogen, fluoro, chloro, bromo, methyl 35 or methoxy; and n is 1-2, particularly n = 1. Embodiment-018: The methods of the present invention according to embodiment-017, wherein L is O and n = 1-2, R2is preferably selected from fluoro, chloro, bromo, methyl or methoxy; preferably PI External 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4-Me, 2-Me, 3-OMe, 4-OMe, 2,4-di- fluoro, or 3,4-di-fluoro. Embodiment-019: The methods of the present invention according to embodiment-017, wherein L is NH and n = 1-2, R2is selected from fluoro, chloro, bromo, methyl or methoxy; preferably 2-F, 3- 5 F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4-Me, 2-Me, 3-OMe, 4-OMe, 2,4-di-fluoro, or 3,4-di-fluoro. Embodiment-020: The methods of the present invention according to embodiment-017, L is S and n = 1-2, R2is preferably selected from fluoro, chloro, bromo, methyl or methoxy; preferably 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-Me, 3-Me, 4-Me, 2-Me, 3-OMe, 4-OMe, 2,4-di-fluoro, 10 or 3,4-di-fluoro. Embodiment-021: The methods of the present invention according to any of the embodiments 002, 004 and 006, wherein for the compound of Formula (VII), R1may be selected from CF3 or CF2Cl, preferably CF3, and R4may be selected from Cl, Br, C1-C3 alkoxy or O-C(O)-CF3. Embodiment-022: The methods of the present invention according to embodiment 021, wherein 15 R1is CF3 and R4is preferably Cl, OMe, OEt, or O-C(O)-CF3. Embodiment-023: The methods of the present invention according to embodiment 022, wherein R1is CF3 and R4is preferably OEt or O-C(O)-CF3. Embodiment-024: The methods of the present invention according to any of the embodiments 003, 005 and 006, wherein for the compound of Formula (VIII) and Formula (IX), X is preferably fluoro 20 or bromo. Embodiment-025: The methods of the present invention according to any of the embodiments 001, 002, 003, 004, 005 and 006, wherein the solvent can be selected from aliphatic or aromatic hydrocarbon, halogenated hydrocarbon, ethers, cyclic ethers, cyclic esters, cyclic carbonate ester, nitro based solvents, nitriles, amides, ketones, acids, alcohols, organosulfur, ionic liquids, water or mixture 25 thereof. Embodiment-026: The methods of the present invention according to embodiment-025, wherein the solvent can be selected from but not limited to water, acetonitrile, acetic acid, methanol, ethanol, iso-propanol, butanol, acetone, pentane, hexane, heptane, octane, nonane, decane, dodecane, cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane; 30 dichloromethane, dichloroethane (ethylene dichloride), chloroform, ethyl acetate, iso-propyl acetate, toluene, xylene, mesitylene, benzene, nitro benzene, nitro methane, diethyl ether, diisopropyl ether, t- butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglyme, diglyme, methoxy-methane, methoxy-ethane, ethoxy-ethane, di-methoxyethane, di-ethoxyethane, N,N- dimethylformamide, dimethyl sulfoxide, sulfolane, carbondisulfide, N-methyl-2-pyrrolidone, 35 propylene carbonate, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphortriamide, 1,3-dimethyl-2-imidazolidinone or of combinations thereof. PI External Embodiment-027: The methods of the present invention according to any of the embodiments 001, 002, 003, 004, 005, and 006, wherein the base, if used, can be selected from an inorganic or organic base such as alkali metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal phosphate, alkali metal hydride, 5 alkali metal alkoxide, alkaline earth metal alkoxide, ethylamine, triethylamine, isopropylamine diisopropylamine, triisopropylamine, pyridine, picoline, piperidine, methylmorpholine, N- methylpiperidine N,N-(dimethylamino)pyridine (DMAP), lutidine, collidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, (TBD), 2,3,4,6,7,8,9,10-octahydropyrimidol[1,2-a]azepine (DBU) 1,5-diazabicyclo[4.3.0]non-5-ene 10 (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), or triethylenediamine. Embodiment-028: The step-a of the present methods according to any of the embodiments 001, 002, 005 and 006, wherein the halogenating agent can be selected from but not limited to F2, Cl2, Br2, I2, Br2 in acetic acid, N-bromosuccinimide, copper bromide (CuBr2), HBr, NaBr, NH4Br, phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), a mixture of NH4Br and potassium 15 peroxymonosulfate sulfate, Trimethylphenylammonium tribromide, N-chlorosuccinimide, phosphorus trichloride (PCl3), phosphorus pentachloride (PCl5), sulfonyl chloride (SOCl2), sulfuryl chloride (SO2Cl2), selenium oxychloride, benzyltrimethylammonium dichloroiodate, or trichloroisocyanuric acid. Embodiment-029: The methods of the present invention according to embodiment-028, wherein 20 the halogenating agent can be selected from Br2, N-bromosuccinimide, Cl2, or N-chlorosuccinimide. Embodiment-030: The methods of the present invention according to embodiments 028 and 029, wherein the halogenating agent is preferably selected from Br2 or Cl2 and particularly Br2. Embodiment-031: The methods of the present invention according to any of the embodiments 001, 002, 005 and 006, wherein the halogenating agent can be used in the presence of a catalyst selected 25 from but not limited to p-toluenesulfonic acid, aluminium chloride (AlCl3), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate. Embodiment-032: The step-a of the present methods according to any of the embodiments 001, 002, 005 and 006, wherein the solvent can be selected from but not limited to dichloromethane, dichloroethane (ethylene dichloride), chloroform, acetonitrile, diethyl ether, methyl tertiary-butyl ether, 30 tetrahydrofuran, 2-methyl-tetrahydrofuran, ethyl acetate, methanol, ethanol, n-propanol, isopropanol, acetic acid or water or a mixture thereof. Embodiment-033: The methods of the present invention according to embodiment-032, wherein the solvent can be selected from dichloromethane, dichloroethane (ethylene dichloride), chloroform, methanol, or methyl tertiary-butyl ether. 35 Embodiment-034: The methods of the present invention according to any of the embodiments 001, 002, 005 and 006, wherein in step-a: PI External i. the halogenating agent is selected from F2, Cl2, Br2, I2, Br2in acetic acid, N-bromosuccinimide, copper bromide (CuBr2), HBr, NaBr, NH4Br, phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), a mixture of NH4Br and potassium peroxymonosulfate sulfate, Trimethylphenylammonium tribromide, N-chlorosuccinimide, phosphorus trichloride (PCl3), 5 phosphorus pentachloride (PCl5), sulfonyl chloride (SOCl2), sulfuryl chloride (SO2Cl2), selenium oxychloride, benzyltrimethylammonium dichloroiodate, or trichloroisocyanuric acid. ii. the catalyst, if used, is selected from p-toluenesulfonic acid, aluminium chloride (AlCl3), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate 10 iii. the solvent is selected from dichloromethane, dichloroethane (ethylene dichloride), chloroform, acetonitrile, diethyl ether, methyl tertiary-butyl ether, tetrahydrofuran, 2-methyl-tetrahydrofuran, ethyl acetate, methanol, ethanol, n-propanol, isopropanol, acetic acid or water or a mixture thereof. Embodiment-035: The step-a of the present methods according to any of the embodiments 001, 002, 15 005 and 006, when carried out in the presence of an alcohol solvent selected from methanol, ethanol, propanol or isopropanol and a halogenating agent selected from Br2 or Cl2, the halogenation of formula (VI) to formula (V) may proceed in the following manner, , wherein R6is Me, Et, n-Pr or i-Pr and R5ais selected from Br or Cl, wherein an intermediate compound 20 of formula (X) is optionally isolated. Embodiment-036: The step-a of the methods of the present invention according to any of the embodiments 001, 002, 005 and 006, wherein halogenation can be performed at a temperature between 0-120 °C, particularly between 0-60 °C and more particularly, between 0-30 °C. Embodiment-037: The step-b of the present methods according to any of the embodiments 001, 25 002, 005 and 006, wherein the base used for the alkylation reaction can be selected from but not limited to sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, 1,5,7- triazabicyclo[4.4.0]dec-5-ene, pyridine, picoline or 1,4-diazabicyclo[2.2.2]octane. Particularly, it can be selected from sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate. Embodiment-038: The step-b of the present methods according to any of the embodiments 001, 30 002, 005, 006 and 035, wherein the alkylation can also be carried out in the presence of a catalyst such as sodium iodide, potassium iodide, or tetra alkylammonium iodide. PI External Embodiment-039: The step-b of the present methods according to any of the embodiments 001, 002, 005, and 006, wherein the solvent can be chosen from but not limited to acetone, acetonitrile, diethyl ether, methyl ethyl ketone, methanol, ethanol, 1,4-dioxane, dichloromethane, toluene, N,N- dimethylformamide (DMF) or water or a mixture thereof; particularly the solvent is preferably selected 5 from acetone, acetonitrile, toluene, ethanol or methanol. Embodiment-040: The step-b of the present methods according to any of the embodiments 001, 002, 005, and 006, wherein in step-b, i. the base is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, pyridine, picoline or 1,4- 10 diazabicyclo[2.2.2]octane. Particularly, it can be selected from sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate; ii. the catalyst if used, is selectee from sodium iodide, potassium iodide, or tetra alkylammonium iodide; iii. the solvent is selected from acetone, acetonitrile, diethyl ether, methyl ethyl ketone, 15 methanol, ethanol, 1,4-dioxane, dichloromethane, toluene, N,N-dimethylformamide (DMF) or water or a mixture thereof. Embodiment-041: The step-b of the present methods according to any of the embodiments 001, 002, 005, and 006, wherein the alkylation was carried out at a temperature ranging from 0 °C to 160 °C, particularly from 0 °C to 85 °C, more particularly 0 °C to 40°C. 20 Embodiment-042: The methods of the present invention according to any of the embodiments 001, 002, 005 and 006, wherein the reagent hydroxylamine used in step-c can be either in an aqueous form or in a solid form such as a salt form. Embodiment-043: The methods of the present invention according to embodiment-042, wherein the salt form can be selected from halide, carboxylate, acetate, trifluoroacetate, sulfonate, 25 trifluoromethanesulfonate, sulfate, preferably it is a hydrochloride salt or hydrogen sulfate salt. Embodiment-044: The methods of the present invention according to embodiment-042, wherein the reagent hydroxylamine is 50% aqueous hydroxylamine. Embodiment-045: The methods of the present invention according to embodiment-042, wherein the reagent hydroxylamine is hydroxylamine hydrochloride salt. Hydroxylamine hydrochloride is 30 soluble in polar organic solvents and is more stable to oxidation and is easy to handle on large quantity as compared to free hydroxylamine or aqueous hydroxylamine, and as a result, step-c of the present method was carried out using hydroxylamine hydrochloride. When hydroxylamine hydrochloride was used, step-c was carried out in the presence of a base to neutralize the hydrochloride salt. Embodiment-046: The methods of the present invention according to any of the embodiments 35 001, 002, 005, 006 and 045, wherein the base used in step-c can be selected from alkali metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, triethylamine, diisopropylamine, or triisopropylamine, pyridine, or picoline. PI External Embodiment-047: The methods of the present invention according to embodiment-046, wherein the base can be selected from sodium carbonate, sodium bicarbonate, potassium carbonate or triethylamine. Embodiment-048: The methods of the present invention according to any of the embodiments 5 001, 002, 005 and 006, wherein step-c was performed in a suitable solvent selected from but not limited to alcohol, diethyl ether, N,N-dimethylformamide, tetrahydrofuran or water or a mixture thereof. Embodiment-049: The methods of the present invention according to embodiment-048, wherein the solvent can be selected from ethanol, methanol, isopropanol or water or a mixture thereof. Embodiment-050: The methods of the present invention according to any of the embodiments- 10 001, 002, 005 and 006, wherein in the step-c: i. the base if used, is selected from alkali metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, triethylamine, diisopropylamine, or triisopropylamine, pyridine, or picoline. ii. the solvent is selected from alcohol, ethanol, methanol, isopropanol, diethyl ether, N,N- 15 dimethylformamide, tetrahydrofuran or water or mixture thereof. Embodiment-051: The suitable temperature to carry out step-c of the present methods according to any of the embodiments 001, 002, 005 and 006, can vary from 0 °C to 50 °C, particularly from 0 °C to 30 °C, when it is performed with aqueous hydroxylamine. Embodiment-052: The suitable temperature to carry out step-c of the present methods according 20 to any of the embodiments 001, 002, 005 and 006, can vary from 25 °C to 160 °C, particularly from 25 °C to 80 °C, when it is performed with hydroxylamine salt preferably hydroxylamine hydrochloride. Embodiment-053: The step-d of the present methods according to any of the embodiments 002, 004 and 006, wherein the dioxime compound of Formula (II) was reacted with the compound of Formula (VII) without using a base, depending on the reactivity of the reactants used. Once the reactants 25 are consumed, the reaction mixture is subjected to acidic treatment under heating condition to obtain the compound of Formula (I) in a single step. Embodiment-054: The step-d of the present methods according to any of the embodiments 002, 004 and 006, wherein the dioxime compound of Formula (II) was reacted with the compound of Formula (VII) using a base, depending on the reactivity of the reactants used. Once the reactants are 30 consumed, the reaction mixture is subjected to acidic treatment under heating condition to obtain the compound of Formula (I) in a single step. Embodiment-055: The methods of the present invention according to embodiment-054, wherein the base in step-d can be chosen from but not limited to an alkali metal alkoxide or alkaline earth metal alkoxide. 35 Embodiment-056: The methods of the present invention according to embodiment-055, wherein the base in step-d is preferably selected from sodium ethoxide or sodium methoxide. PI External Embodiment-057: The methods of the present invention according to embodiments-053 and 054, wherein the acid used for the acidic treatment in step-d, can be selected from but not limited to sulphuric acid, hydrochloric acid, or hydrobromic acid. Embodiment-058: The methods of the present invention according to embodiment-057, wherein 5 the acid in step-d can be selected from hydrochloric acid and particularly from an aqueous hydrochloric acid. Embodiment-059: The step-d of the present methods according to any of the embodiments 002, 004 and 006, wherein the step-d is carried out in the presence of solvent which includes alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, or N,N-dimethylformamide or water. 10 Embodiment-060: The methods of the present invention according to embodiment-059, wherein the solvent in step-d is preferably selected from methanol, ethanol, isopropanol, tetrahydrofuran or water and particularly, it is selected from methanol, ethanol or tetrahydrofuran. Embodiment-061: The methods of the present invention according to any of the embodiments 002, 004 and 006, wherein in the step-d: 15 i. the base if used, is selected from an alkali metal alkoxide or alkaline earth metal alkoxide; ii. the acid is selected from sulphuric acid, hydrochloric acid, or hydrobromic acid; and iii. the solvent is selected from alcohol, methanol, ethanol, tetrahydrofuran, 2- methyltetrahydrofuran, acetonitrile, or N,N-dimethylformamide or water. 20 Embodiment-062: The step-d of the present methods according to any of the embodiments 002, 004 and 006, wherein the reaction temperature is between 0 °C-120 °C, preferably between 0 °C-90 °C. Embodiment-063: The step-i of the present methods according to any of the embodiments 003, 005 and 006, wherein the catalyst can be selected from but not limited to aluminium chloride (AlCl3), iron chloride (FeCl3), copper bromide (CuBr), or a metal triflate and preferably it is selected from 25 aluminium chloride. Embodiment-064: The step-i of the present methods according to any of the embodiments 003, 005 and 006, wherein the suitable solvent used for acetylation can be chosen from but not limited to dichloromethane, dichloroethane (ethylene dichloride), 1,4-dioxane, toluene or benzene. Embodiment-065: The step-i of the present methods according to any of the embodiments 003, 30 005 and 006, wherein the reaction temperature is between 0 °C -100 °C and particularly between 0 °C -30 °C. Embodiment-066: The step-ii of the present methods according to any of the embodiments 003, 005 and 006, wherein halo to cyano conversion was performed using the cyanide source selected from an alkali metal cyanide and the catalyst selected from a phase transfer catalyst, in a solvent at a 35 temperature ranging from 25 °C -150 °C. Embodiment-067: The methods of the present invention according to embodiment-066, wherein the alkali metal cyanide is sodium cyanide or potassium cyanide. PI External Embodiment-068: The methods of the present invention according to embodiment-066, wherein the phase transfer catalyst is preferably selected from tetraalkylammonium salt, tetraalkylphosphonium salt or crown ether. Embodiment-069: The methods of the present invention according to embodiment-066 or 5 embodiment-068, wherein the phase transfer catalyst can be tetraalkylammonium halide and particularly, tetrabutylammonium bromide (Bu4N+Br-) tetrabutylammonium chloride (Bu4N+Cl-), tetraethylammonium chloride (Et4N+Cl-), tetraethylammonium bromide (Et4N+Br-), tetramethylammonium chloride (Me4N+Cl-). Embodiment-070: The step-ii of the present methods according to any of the embodiments 003, 10 005, 006 and 066, wherein when X=F for the compound of Formula (VIII), then step-ii was carried out with alkali metal cyanide selected from sodium cyanide and a phase transfer catalyst selected from tetrabutylammonium bromide or tetraethylammonium chloride in a suitable solvent at a temperature ranging from 25 °C -150 °C, to obtain the desired compound of Formula (VI) in high yield, without using a transition metal catalyst and / or a base or an additive / ligand such as alkyl substituted 15 ethylenediamine. As a consequence, the present methods according to embodiments 003, 005 and 006, are convenient, minimize operational difficulties and cost effective over known methods. Embodiment-071: The step-ii of the present methods according to any of the embodiments 003, 005, and 006, can be performed in the presence of a metal catalyst, wherein the cyanide source may be selected from alkali metal cyanide or alkali metal hexacyanoferrate (II) or its hydrates, preferably from 20 sodium or potassium cyanide, sodium or potassium hexacyanoferrate (II) or its hydrates. Embodiment-072: The step-ii of the present methods according to embodiment 071, wherein the metal catalyst may be selected from copper or copper (I) salt in the presence of a suitable ligand, wherein the copper (I) salt, can be CuCl, CuBr and CuI, and the suitable ligand includes but not limited to dialkylethylenediamine, tetralkylethylenediamine, 1,10-phenanthroline, or bipyridine. Particularly, the 25 ligand may be chosen from 1,10-phenanthroline, bipyridine, bis(1,2-diphenylphosphino)ethane, triarylphosphine, triphenylphosphine, ethylenediamine, N,N’-dimethylethylenediamine, N,N,N’,N’- tetramethylethylenediamine. An additive such as potassium iodide or tetraalkylammonium halide may also be used. Embodiment-073: The step-ii of the present methods according to any of the embodiments 003,30 005, 006 and 071, wherein the catalyst may be selected from palladium source but not limited to Pd- nanoparticles, Pd on activated charcoal, 10% Pd / C or 5% Pd / C. Embodiment-074: The cyanation reaction mentioned in step-ii of the present methods according to any of the embodiments 004, 005-006 and embodiments 071-073, may be performed in the presence of one or more optional base selected from alkali metal carbonate, alkaline earth metal carbonate, 35 organic amine, triethylamine or a mixture thereof, preferably the useful base is selected from sodium carbonate, potassium carbonate, triethylamine or mixture thereof. PI External Embodiment-075: The step-ii of the present methods according to embodiments 003, 005 and 006, wherein when X = Br for the compound of Formula (VIII), it may be carried out with potassium hexacyanoferrate trihydrate in the presence of CuI, and a ligand such as N,N’-dimethylethylenediamine in a suitable solvent; or it may be carried out with potassium hexacyanoferrate trihydrate in the presence 5 of 10% Pd / C and a mixture of base selected from sodium carbonate and triethylamine, in a suitable solvent. Embodiment-076: The step-ii of the present methods according to any of the embodiments 003, 005-006 and embodiment-066 and embodiment-071, wherein the solvent can be chosen from polar solvents but not limited to water, alcohol, acetonitrile, dimethylformamide, dimethylacetamide, N- 10 methylpyrrolidinone, dimethylsulfoxide or a mixture thereof, and particularly, the solvent is dimethylformamide, N-methylpyrrolidinone, n-butanol or a mixture of n-butanol and N- methylpyrrolidinone. Embodiment-077: The step-ii of the present methods according to embodiments 003, 005, 006 and embodiment-066 and embodiment-071, wherein the temperature can vary between 25 °C - 150 °C 15 and particularly, it is in the range of 25 °C - 40 °C during the addition of cyanide and then increased to 100 °C -150 °C. Embodiment-078: The methods of the present invention according to embodiments-001-006, wherein the reaction time is not critical and is depends on the batch size, temperature, type of reaction, solvent and the used reagents and is usually between few minutes to few hours. 20 Embodiment-079: The present invention provides a method for the synthesis of a compound of formula (V) comprising the steps of: a-1. reacting a compound of formula (VI) with a halogenating agent selected from chlorine or bromine in the presence of an alcoholic solvent to obtain a compound of formula (Z); , wherein Rxand RY25 represent C1-C6-alkyl; or Rxand RYtogether with the atom to which they are attached may form 5 or 6 membered ring and X represents Br or Cl; a-2. obtaining the compound of formula (V) by reacting the compound of formula (Z) with an acid; PI External , wherein Rxand RYrepresent C1-C6-alkyl; or Rxand RYtogether with the atom to which they are attached may form a 5- or 6- membered ring and X represents Br or Cl. Embodiment-080: The alcoholic solvent mentioned in the step a-1 of embodiment 079, can be 5 selected from methanol, ethanol, propanol, isopropanol, ethylene glycol or propylene glycol; preferably methanol. Embodiment-081: The acid mentioned in the step a-2 of embodiment 079, can be selected from mineral acids such as hydrochloric acid or sulphuric acid. Embodiment-082: The steps a-1 and a-2 can be carried out at a temperature ranging from 25°C - 10 125°C. Embodiment-083: The present invention provides a method for preparing a compound of Formula (II) or its N-oxides or an agriculturally acceptable salt thereof, wherein, 15 L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, 20 comprising the step of: reacting a compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain the dioxime compound of Formula (II) (step-c), . PI External Embodiment-084: The present method for preparing the compound of formula (II) from the compound of formula (III) according to embodiment-083, wherein hydroxylamine, base, solvent and reaction temperature for performing said conversion can be according to embodiment-042 to 5 embodiment-052. Embodiment-085: The present methods for preparing the compound of Formula (I) or its intermediate compound of Formula (II), Formula (III), or Formula (VI) as disclosed herein, wherein the steps can be carried out in a batch, semi-continuous or continuous reaction mode, specifically also under semi-continuous flow or continuous flow reaction conditions. 10 The person skilled in the art knows the best work-up of the reaction mixtures after the end of the respective reactions. The work-up is usually carried out by isolation of the product, and optionally washing with solvent, and further optionally drying of the product if useful or required. The isolation of the reaction product can be carried out by a technique which includes but is not limited to decantation, filtration, centrifugation, evaporation, liquid-liquid extraction, distillation, 15 recrystallization, chromatography and the like or a combination thereof. The reaction steps according to the invention are generally carried out under atmospheric pressure. Alternatively, however, it is also possible to work the method steps of the present method under reduced pressure or higher pressure. The invention is further illustrated by the following examples which are provided to be exemplary of 20 the invention, and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. Although the subject matter has been described in considerable detail with reference to certain examples and implementations thereof, other implementations are possible. 25 EXAMPLES The disclosure will now be illustrated with the working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one ordinary person skilled in the art to which this disclosure 30 belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may apply. PI External The present invention for preparing a compound of Formula (I) and its intermediate compound of formula (II) can be illustrated with the representative scheme 1 as provided below: Scheme-1 5 wherein R1, R2, L and n are as described above. Experimental Procedure Step i: Synthesis of 1-(4-fluorophenyl)ethan-1-one 10 To a solution of fluorobenzene (10 g, 104 mmol) in ethylene dichloride (EDC) (50 mL), aluminium chloride (16.32 g, 122 mmol) was added at 25-30 °C under nitrogen atmosphere. The reaction mass was cooled to 0-5 °C, and then acetyl chloride (8 mL, 112 mmol) was added in a dropwise manner. The reaction mass was allowed to stir for 12 hours at 25-30 °C. After completion of the reaction, the reaction mixture was quenched by addition of a saturated sodium bicarbonate solution (250 mL). The reaction 15 mixture was then extracted with ethylene dichloride (2 x 50 mL) and the combined organic layer was washed with brine (50 mL) and concentrated under reduced pressure to afford 1-(4-fluorophenyl)ethan- 1-one (14.25 g, 99.14 % yield) as a colourless liquid. 1H-NMR (400 MHz, CDCl3) δ 7.94-7.89 (m, 2H), 7.08-7.02 (m, 2H), 2.51 (s, 3H); GC-MS: m / z 138.1. Step i: Preparation of 4'-bromoacetophenone PI External To a solution of bromobenzene (100 g, 637 mmol) in ethylene dichloride (EDC) (500 mL), aluminium chloride (102 g, 764 mmol) was added at 25-30 °C under nitrogen atmosphere. The reaction mass was cooled to 0-5 °C and then acetyl chloride (54.5 mL, 764 mmol) was added in a dropwise manner. The 5 reaction mass was allowed to stir for 12 hours at 20-30 °C. After completion of the reaction, the reaction mixture was quenched by pouring it into a saturated sodium bicarbonate solution (1000 mL). The reaction mixture was extracted with ethylene dichloride (2 x 250 mL), and the combined organic layer was washed with brine (500 mL) and concentrated under reduced pressure to afford 4'- bromoacetophenone (101.3 g, 79.91% yield) as a white solid. 101H-NMR (400 MHz, DMSO-D6) δ 7.88-7.85 (m, 2H), 7.74-7.70 (m, 2H), 2.56 (s, 3H); GC-MS: m / z 197.8. Step ii: Preparation of 4-acetylbenzonitrile Method 1: 15 To a stirred suspension of 1-(4-fluorophenyl) ethan-1-one (10 g, 72.4 mmol) in dimethylformamide (DMF) (50 mL), tetrabutylammonium bromide (TBAB), (2.3 g, 7.2 mmol) and sodium cyanide (7.1 g, 145 mmol) were added at 25-30 °C under nitrogen atmosphere. The reaction mixture was heated at 130- 140 °C and stirred for 10 hours. After completion of the reaction, the reaction mixture was cooled to 25-30 °C and quenched by addition of water (150 mL), and finally extracted with methyl tert-butyl ether 20 (MTBE) (3 X 100 mL). The combined organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to afford 4- acetylbenzonitrile (8.3 g, 78.99%) as an off-white solid. 1H-NMR (400 MHz, DMSO-D6) 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 2.61 (s, 3H) Method 2: 25 To a stirred suspension of 1-(4-fluorophenyl) ethan-1-one (10 g, 72.4 mmol) in N-methyl-2-pyrrolidone (NMP) (40 mL) were added tetraethylammonium chloride (Et4NCl) (2.4 g, 14.48 mmol) and sodium cyanide (7.1 g, 145 mmol) at 25-30 °C under nitrogen atmosphere. The reaction mixture was heated at 100 °C and stirred for 10 hours. After completion of reaction, the mixture was cooled at 25-30 °C and quenched with water (50 mL) and extracted with methyl tert-butyl ether (MTBE) (3 X 80 mL). The PI External combined organic layer was washed with brine (50 mL), dried over Na2SO4and concentrated under reduced pressure to afford 4-acetylbenzonitrile (8.5 g, 81.0%) as an off-white solid. 1H-NMR (400 MHz, DMSO-D6) 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 2.61 (s, 3H) Method-3 5 To a stirred suspension of 1-(4-bromophenyl)ethan-1-one (10 g, 49.2 mmol) and N-methyl-2- pyrrolidone (NMP) (9.48 mL, 98 mmol) in n-butanol (60 mL), potassium ferrocyanide trihydrate (10.40 g, 24.62 mmol) and N,N'-dimethylethylenediamine (5.30 mL, 49.2 mmol) were added at 25-30 °C. The reaction mixture was stirred for 5 min, then copper (I) iodide (CuI) (1.875 g, 9.85 mmol) was added at 25-30 °C. The reaction mixture was heated at 130-135 °C and stirred for 12 hours. After completion of 10 the reaction, the reaction mixture was cooled to 25 °C and filtered through a celite bed. The celite bed was washed with ethyl acetate (50 mL), collective filtrate was diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was washed with brine (2 x 100 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford a brown coloured solid material. This material was further stirred in cyclohexane (100 mL) for 15 1 hour at 25 °C, filtered and dried under reduced pressure to afford 4-acetylbenzonitrile (5.4 g, 74.05 % yield) as an off-white sold. 1H-NMR (400 MHz, DMSO-D6) 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 2.61 (s, 3H) Method-4 To a stirred solution of 1-(4-bromophenyl)ethan-1-one (10.0 g 50.2 mmol) in dimethylformamide 20 (DMF) (50 mL), sodium carbonate (10.65 g, 100 mmol) and triethylamine (TEA) (14.01 mL, 100 mmol) were added at 25-30 °C. The reaction mixture was stirred for 5 min, then potassium ferrocyanide trihydrate (5.31 g, 12.56 mmol) and 10% Pd / C (50% wet, 2.67 g, 2.51 mmol) were added at 25-30 °C. The reaction mixture was heated to 140 °C and stirred for 4 hours. After completion of the reaction, the reaction mixture was cooled to 20-30 °C, diluted with ethyl acetate (30 mL) and filtered through celite 25 bed. The collected filtrate was washed with water (2 X 50 mL) and brine solution (50 mL). The organic phase was dried with anhydrous sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure. The crude product obtained was purified by silica gel chromatography with eluent ethyl acetate / n-hexane to afford an off white solid of 4-acetylbenzonitrile (7.0 g, 62.39% yield (assay basis). 1H-NMR (400 MHz, DMSO-D6) 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 2.61 (s, 3H). 30 PI External Condition 1: To a stirred solution of 4-acetylbenzonitrile (10 g, 68.9 mmol) in methyl tert-butyl ether (MTBE) (200 mL), was added a solution of bromine (4.26 ml, 83 mmol) in MTBE (50 mL) at 0 °C in a dropwise 5 manner. After complete addition of the bromine solution, the reaction mixture was stirred for 20 minutes, and a 2ndlot of bromine (1.07 mL, 20.67 mmol) solution in MTBE (50 mL) was added in a dropwise manner. After that, the reaction mixture was warmed to 25-30 °C and stirred for 8 hour. After completion of reaction, the reaction mixture was concentrated under reduced pressure, and the resulting crude solid was added into isopropyl alcohol (IPA) (20 mL), stirred for 1 hour at 25-30 °C and filtered 10 to obtain a wet cake. The wet cake was then dried in a vacuum tray dryer (VTD) under reduced pressure to afford 4-(2-bromoacetyl)benzonitrile (10 g, 64.7% yield) as an off-white solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.13 (dt, J = 8.5, 1.8 Hz, 2H), 8.06-8.02 (m, 2H), 5.00 (s, 2H); MS: m / z 226.3 [M+2]+. Condition 2: 15 To a stirred solution of 4-acetylbenzonitrile (100 g, 689 mmol) in dichloromethane (DCM) (2 L), was added a solution of bromine (42.6 mL, 826 mmol) in DCM (500 mL) at 25-30 °C in a dropwise manner. After the addition, the reaction mixture was stirred at 25-30 °C for 4 hours. After completion of the reaction, the reaction mixture was quenched with water (500 mL). The organic phase was separated and washed it with brine solution (200 mL). The obtained organic layer dried over Na2SO4 and concentrated 20 under reduced pressure. The resulting crude solid was added into isopropyl alcohol (IPA) (200 mL), stirred for 1 hour at 25-30 °C and filtered to obtain a wet cake. The wet cake was dried in VTD under reduced pressure to afford 4-(2-bromoacetyl)benzonitrile (118 g, 76.4 % yield) as an off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.13 (dt, J = 8.5, 1.8 Hz, 2H), 8.06-8.02 (m, 2H), 5.00 (s, 2H); MS: m / z 226.3 [M+2]+. 25 Condition 3: PI External To a stirred solution of 4-acetylbenzonitrile (10 g, 67.5 mmol) in methanol (100 mL), bromine (12.11 g, 74.3 mmol) was added in a dropwise manner at 25-28 °C. After the addition, the reaction mixture was stirred for 10 h at 25-35°C. After completion of the reaction, the reaction mixture was quenched with saturated sodium bicarbonate solution (100 mL). The reaction mixture was then concentrated under 5 reduced pressure to distil out methanol and the obtained residue was extracted with ethyl acetate (2 x 250 mL). The collective organic layer was concentrated under reduced pressure to afford 4-(2-bromo- 1,1-dimethoxyethyl)benzonitrile (18.0 g, 96.7% yield) as light green colour solid. 1H-NMR (400 MHz, CDCl3) δ 7.69-7.66 (d, J = 8.0 Hz, 2H), 7.64-7.61 (d, J = 8.0 Hz, 2H), 3.58 (s, 2H), 3.20 (s, 6H) 10 To a stirred solution of 4-(2-bromo-1,1-dimethoxyethyl)benzonitrile (2 g, 7.40 mmol) in water (10 ml), hydrochloric acid (2.121 ml, 24.43 mmol) was added at 25-40 °C. The reaction mixture was then stirred for 6 h at 25-40°C. After completion of the reaction, the reaction mixture was filtered and washed with water (2 ml). The obtained solid was dried under reduced pressure to afford 4-(2- 15 bromoacetyl)benzonitrile (1.45 g, 87% yield) as off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.13 (dt, J = 8.5, 1.8 Hz, 2H), 8.06-8.02 (m, 2H), 5.00 (s, 2H); MS: m / z 226.3 [M+2]+Step-b: Preparation of 4-(2-(4-fluorophenoxy)acetyl)benzonitrile 20 To a stirred solution of 4-fluorophenol (2.50 g, 22.32 mmol) in acetone (25 mL) was charged potassium carbonate (4.63 g, 33.5 mmol) and stirred for 10 minutes at 25-30 °C. The reaction mixture was then cooled to 0-5 °C followed by the addition of a solution of 4-(2-bromoacetyl)benzonitrile (5.0 g, 22.32 mmol) in acetone (25 mL). After completion of the addition, the reaction mixture was warmed to 25- 30 °C and stirred for 12 hours. After completion of the reaction, the reaction mixture was filtered, and 25 the filtrate was concentrated under reduced pressure at 45 °C. The obtained residue was diluted with MTBE (10 mL) and stirred at 25-30 °C for 1 hour. The resulting reaction mixture was filtered, to obtain a wet cake. The wet cake was then washed with hexane (200 mL) and dried under vacuum at 40 °C for 4 hours to afford 4-(2-(4-fluorophenoxy)acetyl) benzonitrile (3.0 g, 52.7% yield) as an off-white solid. PI External 1H-NMR (400 MHz, DMSO-D6) δ 8.17-8.14 (m, 2H), 8.08-8.04 (m, 2H), 7.14-7.06 (m, 2H), 7.06-6.93 (m, 3H), 6.75-6.70 (m, 1H), 5.58 (s, 2H); MS: m / z 254.85 [M+1]+. Step-b: Preparation of 4-((4-fluorophenyl)glycyl)benzonitrile 5 To a stirred solution of 4-(2-bromoacetyl)benzonitrile (5 g, 22.32 mmol) in ethanol (25 mL), were charged sodium bicarbonate (1.875 g, 22.32 mmol) and 4-fluoroaniline (2.119 ml, 22.32 mmol) at 10- 15 °C. The reaction mixture was warmed to 25-30 °C and stirred for 10 hours. After completion of the reaction, the reaction mixture was cooled at 0 °C and diluted with water (250 mL) and stirred for 30 min. The reaction mixture was then filtered and dried under vacuum to afford 4-((4- 10 fluorophenyl)glycyl)benzonitrile (5.3 g, 93.4% yield) as a yellow solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.19 (d, J = 8.6 Hz, 2H), 8.03 (d, J = 8.3 Hz, 2H), 6.94-6.88 (m, 2H), 6.70-6.65 (m, 2H), 5.86 (s, 1H), 4.69 (s, 2H); MS: m / z 255.00 [M+1]+Step-c: Preparation of 4-(2-(4-fluorophenoxy)-1-(hydroxyimino)ethyl)-N'- hydroxybenzimidamide 15 Condition 1: By using 50% aqueous solution of hydroxylamine To a stirred solution of 4-(2-(4-fluorophenoxy)acetyl)benzonitrile (4 g, 15.67 mmol) in ethanol (40 mL), was added a 50% aqueous solution of hydroxylamine (2.03 mL, 36.0 mmol) in a drop wise manner at 0-5 °C. The reaction mixture was gradually warmed to 25-30 °C and stirred for 16 hours. After 20 completion of the reaction, the reaction mixture was cooled at 0 °C, diluted with water (200 mL) and stirred for 30 minutes, and filtered. The obtained wet cake was dried in vacuum to afford 4-(2-(4- fluorophenoxy)-1-(hydroxyimino)ethyl)-N'-hydroxybenzimidamide (4 g, 84.1% yield) as an off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 11.95 (s, 1H), 9.69 (s, 1H), 7.64 (q, J = 8.6 Hz, 4H), 7.11-7.06 (m, 25 2H), 6.95-6.92 (m, 2H), 5.81 (bs, 2H), 5.23 (s, 2H); MS: m / z 304.05 [M+1]+ PI External Condition 2: By using hydroxylamine hydrochloride salt To a stirred solution of 4-(2-(4-fluorophenoxy)acetyl)benzonitrile (12.5 g, 48.9 mmol) in methanol (100 mL), was added hydroxylamine hydrochloride (4.34 g, 62.5 mmol) at 25 °C. The reaction mixture was warmed to 65 °C, stirred for 10 hours and then concentrated at 50 °C. The residue was extracted with 5 ethyl acetate (150 mL). The organic layer was washed with water (150 mL) and the collected organic layer was concentrated under reduced pressure. To the resulting residue, were charged methanol (100 mL), hydroxylamine hydrochloride (4.34 g, 62.5 mmol) and triethyl amine (8.71 mL, 62.5 mmol) at 25 °C and stirred for 10 hours. After completion of the reaction, the reaction mixture was cooled to 0 °C, diluted with water (500 mL) and then stirred for 30 minutes and filtered. The obtained wet cake was10 dried under vacuum to afford 4-(2-(4-fluorophenoxy)-1-(hydroxyimino)ethyl)-N'- hydroxybenzimidamide (8 g, 84.38% yield) as an off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 11.95 (s, 1H), 9.69 (s, 1H), 7.64 (q, J = 8.6 Hz, 4H), 7.11-7.06 (m, 2H), 6.95-6.92 (m, 2H), 5.81 (bs, 2H), 5.23 (s, 2H); MS: m / z 304.05 [M+1]+. 4-(2-((4-fluorophenyl)amino)-1-(hydroxyimino)ethyl)-N'- 15 To a stirred solution of 4-((4-fluorophenyl)glycyl)benzonitrile (25.0 g, 98.32 mmol) in methanol (200 mL), was added hydroxylamine hydrochloride (13.12 g, 189 mmol) at 25 °C. The reaction mixture was warmed to 65 °C and stirred for 10 hours. The reaction mixture was concentrated at 50 °C and extracted 20 with ethyl acetate (150 mL). The organic layer was washed with water (150 mL) and the collected organic layer was then concentrated under reduced pressure. To the resulting residue, methanol (150 mL), hydroxylamine hydrochloride (9.84 g, 142 mmol) and triethyl amine (19.73 mL, 142 mmol) were added at 25 °C and stirred for 10 hours. After completion of the reaction, the reaction mixture was cooled to 0 °C, diluted with water (500 mL), stirred for 30 min and then filtered. The obtained wet cake25 was dried under vacuum to afford 4-(2-((4-fluorophenyl)amino)-1-(hydroxyimino)ethyl)-N'- hydroxybenzimidamide (26 g, 87.5 % yield) as an off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 11.65 (s, 1H), 9.67 (s, 1H), 7.64-7.56 (m, 4H), 6.88-6.82 (m, 2H), 6.56-6.50 (m, 2H), 5.81 (m, 3H), 4.33 (d, J = 5.9 Hz, 2H); MS: m / z 303.2 [M+1]+. PI External Step-d: Preparation of 2-(4-fluorophenoxy)-1-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one of Formula (I) 5 Condition 1: By using trifluoracetic anhydride To a stirred solution of 4-(2-(4-fluorophenoxy)-1-(hydroxyimino)ethyl)-N'-hydroxybenzimidamide (18 g, 59.3 mmol) in tetrahydrofuran (180 mL), was added trifluoracetic anhydride (10.1 mL, 71.2 mmol) in a drop wise manner at 0 °C. After complete addition, the mixture was warmed to 25-30 °C and stirred for 16 hours. After completion of the reaction, the resulting mixture was diluted with water (150 mL) 10 and extracted with ethyl acetate (2 x 100 mL). The collective organic layer was distilled off under reduced pressure for solvent recovery. Then water (100 mL) and conc. HCl (100 mL) were added to the solid residue respectively at 25-30 °C. The reaction mass was then heated to 90 °C, and stirred for 16 hours. The reaction mixture was allowed to cool to 25-30 °C, filtered and dried under vacuum. The solid crude product was taken in n-hexane (1.0 L), stirred for 30 minutes, and filtered to obtain a wet 15 cake. The wet cake was dried in a vacuum tray dryer (VTD) at 45 °C under reduced pressure to afford the final product 2-(4-fluorophenoxy)-1-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)ethan-1- one (19.5 g, 90.0 % yield) as an off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.24-8.20 (m, 4H), 7.13-7.08 (m, 2H), 7.03-7.00 (m, 2H), 5.62 (s, 2H); MS: m / z 364.45 [M-1]+. 20 Condition 2: By using ethyl trifluoroacetate and NaOMe in MeOH To a stirred solution of 4-(2-(4-fluorophenoxy)-1-(hydroxyimino)ethyl)-N'-hydroxybenzimidamide (8 g, 26.4 mmol) in ethyl trifluoroacetate (7.76 mL, 61.7 mmol), was added 30% NaOMe in a MeOH solution (18.9 mL, 103 mmol) in a dropwise manner at 25 °C and continued to stir for 2 hours. After completion of the reaction, an aqueous 5N HCl solution (50 mL) was added to the reaction mass and 25 heated to 70 °C. The reaction mixture was further continued to stir for 5 hours at 70 °C. During the reaction, the distillate was collected to recover ethyl trifluoroacetate and methyl trifluoroacetate formed in situ due to trans-esterification, and then, cooled to 20-25 °C and filtered. The resulting solid was washed with water (25 mL) and dried in a vacuum tray dryer (VTD) at 45 °C under reduced pressure PI External to afford the final product 2-(4-fluorophenoxy)-1-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one (5.5 g, 57% yield). 1H-NMR (400 MHz, DMSO-D6) δ 8.24-8.20 (m, 4H), 7.13-7.08 (m, 2H), 7.03-7.00 (m, 2H), 5.62 (s, 2H); MS: m / z 364.45 [M-1]+. 5 Condition 3: To a stirred solution of 4-(2-(4-fluorophenoxy)-1-(hydroxyimino)ethyl)-N'-hydroxybenzimidamide (2 g, 6.59 mmol) in ethyl trifluoroacetate (2.061 g, 14.51 mmol), 30% solution of NaOMe in MeOH (2.97 g, 16.49 mmol, 2.5 equivalent) was added in dropwise manner at 25 to 40 °C and continued to stir for 3 h. After completion of the reaction, an aqueous solution of hydrochloric acid (4.58 ml, 52.8 mmol) in 10 water (10 ml) was added at 40-50°C and further heated to 70-80°C. The reaction mixture was continued to stir for 6 h at 80°C. The reaction mixture was cooled to 20-25°C and filtered. The obtained solid was washed with water (100 mL) and dried under reduced pressure to obtain 2-(4-fluorophenoxy)-1-(4-(5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)ethan-1-one (2.3 g, 95.23 % yield) as off white solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.24-8.20 (m, 4H), 7.13-7.08 (m, 2H), 7.03-7.00 (m, 2H), 5.62 (s, 15 2H); MS: m / z 364.75.1 [M-1]+Step-d: Preparation of 2-((4-fluorophenyl)amino)-1-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one of Formula (I) Condition 1: Using trifluoroacetic anhydride 20 To a stirred solution of 4-(2-((4-fluorophenyl)amino)-1-(hydroxyimino)ethyl)-N'- hydroxybenzimidamide (0.2 g, 0.662 mmol) in tetrahydrofuran (2 mL), trifluoroacetic anhydride (0.1 mL, 0.728 mmol) was added in a dropwise manner at 0 °C. After complete addition, the reaction mixture was warmed to 25-30 °C and stirred for 6 hours. After completion of the reaction, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The collective organic 25 layer was distilled off under reduced pressure for solvent recovery. Then water (5 mL) and conc. HCl (5 mL) were added to the solid residue respectively at 25-30 °C. The reaction mass was heated to 90 °C and stirred for 16 hours. The reaction mixture was then cooled to 25-30 °C, filtered and dried under reduced pressure. The obtained solid product was taken in n-hexane (10 mL), stirred for 30 minutes and filtered to obtain a wet cake. The wet cake was then dried in a VTD at 45 °C under reduced pressure to PI External afford the final product 2-((4-fluorophenyl)amino)-1-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl)phenyl)ethan-1-one (200 mg, 82.76% yield) as a light yellow solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.28-8.22 (m, 4H), 7.05-7.00 (m, 2H), 6.93-6.90 (m, 2H), 4.85 (s, 2H); MS: m / z 366.20 [M+1]+. 5 Condition 2: By using ethyl trifluoroacetate and NaOMe in MeOH To a stirred solution of 4-(2-((4-fluorophenyl)amino)-1-(hydroxyimino)ethyl)-N'- hydroxybenzimidamide (5.0 g, 16.53 mmol) in ethyl trifluoroacetate (5.50 mL, 43.7 mmol), was added 30% NaOMe in a MeOH solution (13.4 mL, 72.9 mmol) in a dropwise manner at 25-35 °C and continued to stir for 3 hours. After completion of the reaction, the reaction mass was added into an 10 aqueous 5N HCl solution (50 mL) and further heated to 70 °C. The reaction was further continued to stir for 5 hours at 70 °C. During the reaction, the distillate was collected to recover ethyl trifluoroacetate and methyl trifluoroacetate formed in situ due to trans-esterification, and then, the reaction mixture was cooled to 20-25 °C and filtered. The solid wet cake was washed with water (25 mL) and dried in a VTD at 45 °C under reduced pressure to afford the final product 2-((4-fluorophenyl)amino)-1-(4-(5- 15 (trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)ethan-1-one (4.9 g, 13.41 mmol, 81.2 % yield) as a light yellow solid. 1H-NMR (400 MHz, DMSO-D6) δ 8.28-8.22 (m, 4H), 7.05-7.00 (m, 2H), 6.93-6.90 (m, 2H), 4.85 (s, 2H); MS: m / z 366.20 [M+1]+.

Claims

PI External CLAIMS:

1. A method for preparing a compound of Formula (I), or its N-oxides or agriculturally acceptable salts thereof,5 wherein, R1is selected from -CHF2, -CF2-Cl or CF3; L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; 10 R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, wherein said method comprising the step of: cyclizing a di-oxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the 15 compound of Formula (I) in a single-step (step-d),, wherein, R4is selected from halogen, OH, C1-C6-alkoxy or O-C(O)-R1.

2. A method for preparing a compound of Formula (I), or its N-oxides or agriculturally acceptable salts thereof,20 wherein, R1is selected from -CHF2, -CF2-Cl or CF3; L is selected from O, NR3or S;PI External R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, 5 wherein said method comprising the steps of: a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V),; b. reacting the compound of Formula (V) with a compound of Formula (IV) and a base in a 10 solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III),; c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (II),15 d. cyclizing the dioxime compound of Formula (II) by reacting it with a compound of Formula (VII), optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (I) in a single-step,, wherein, R4is selected from halogen, OH, C1-C6-alkoxy or O-C(O)-R1.PI External 3. A method for preparing a compound of Formula (II) or its N-oxides or an agriculturally acceptable salt thereof,wherein, 5 L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, 10 wherein said method comprising the step of: reacting a compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain a dioxime compound of Formula (II) (step-c),.

4. A method for preparing a compound of Formula (II), or its N-oxides or agriculturally acceptable 15 salts thereof,, wherein, L is selected from O, NR3or S; R2is selected from hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or C3-C6- 20 cycloalkyl; R3is selected from hydrogen or C1-C6-alkyl; and n is an integer selected from 1-2, wherein said method comprising the steps of:PI External a. halogenating a compound of Formula (VI) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (V),; b. reacting a compound of Formula (IV) with the compound of Formula (V) and a base 5 in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (III),c. reacting the compound of Formula (III) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to obtain the dioxime compound of Formula (II),. 10 5. The method as claimed in any one of the claims 1-2, wherein R1is selected from CF3 or CF2Cl; L is selected from O, NH or S; R2is selected from hydrogen, fluoro, chloro, bromo, methyl or methoxy; and n is 1-2 6. The method as claimed in any one of the claims 2 to 4, wherein the reagent hydroxylamine in step-c is in an aqueous form or in a salt form. 15 7. The method as claimed in claim 6, wherein the salt form is selected from halide (HX), carboxylate, acetate, trifluoroacetate, sulfonate, trifluoromethanesulfonate, or sulfate.

8. The method as claimed in any one of the claims 1-4, wherein the solvent is selected from acetonitrile, acetic acid, methanol, ethanol, iso-propanol, butanol, acetone, pentane, hexane, heptane, octane, nonane, decane, dodecane, cyclobutane, cyclopentane, cyclohexane, 20 cycloheptane, cyclooctane; dichloromethane, dichloroethane (ethylene dichloride), chloroform, chlorobenzene, ethyl acetate, iso-propyl acetate, toluene, xylene, mesitylene, nitro benzene, nitro methane, diethyl ether, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglyme, diglyme, methoxy-methane, methoxy-ethane, ethoxy-PI External ethane, di-methoxyethane, di-ethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, sulfolane, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphortriamide, 1,3-dimethyl-2-imidazolidinone or of combinations thereof.

9. The method as claimed in any one of the claims 1-4, wherein the base is selected from alkali 5 metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal phosphate, alkali metal hydride, alkali metal alkoxide, alkaline earth metal alkoxide, ethylamine, triethylamine, isopropylamine diisopropylamine, triisopropylamine, pyridine, picoline, piperidine, methylmorpholine, N- methylpiperidine N,N-(dimethylamino)pyridine (DMAP), lutidine, collidine,10 tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, 1,5,7- triazabicyclo[4.4.0]dec-5-ene, (TBD), 2,3,4,6,7,8,9,10-octahydropyrimidol[1,2-a]azepine (DBU) 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethylenediamine or of combinations thereof.

10. The method as claimed in claim 2 or claim 4, wherein in step-a: 15 i. the halogenating agent is selected from F2, Cl2, Br2, I2, Br2 in acetic acid, N- bromosuccinimide, copper bromide (CuBr2), HBr, NaBr, NH4Br, phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), a mixture of NH4Br and potassium peroxymonosulfate sulfate, Trimethylphenylammonium tribromide, N- chlorosuccinimide, phosphorus trichloride (PCl3), phosphorus pentachloride (PCl5), 20 sulfonyl chloride (SOCl2), sulfuryl chloride (SO2Cl2), selenium oxychloride, benzyltrimethylammonium dichloroiodate, or trichloroisocyanuric acid. ii. the catalyst, if used, is selected from p-toluenesulfonic acid, aluminium chloride (AlCl3), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate 25 iii. the solvent is selected from dichloromethane, dichloroethane (ethylene dichloride), chloroform, acetonitrile, diethyl ether, methyl tertiary-butyl ether, tetrahydrofuran, 2- methyl-tetrahydrofuran, ethyl acetate, methanol, ethanol, n-propanol, isopropanol, acetic acid or water or a mixture thereof.

11. The method as claimed in claim 2 or claim 4, wherein in step-b, 30 i. the base is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, pyridine, picoline or 1,4- diazabicyclo[2.2.2]octane; ii. the catalyst if used, is selectee from sodium iodide, potassium iodide, or tetra alkylammonium iodide;PI External iii. the solvent is selected from acetone, acetonitrile, diethyl ether, methyl ethyl ketone, methanol, ethanol, 1,4-dioxane, dichloromethane, toluene, N,N-dimethylformamide (DMF) or water or a mixture thereof.

12. The method as claimed in claim 2, or claim 3 or claim 4, wherein in step-c, 5 i. the base if used, is selected from alkali metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, triethylamine, diisopropylamine, or triisopropylamine, pyridine, or picoline. ii. the solvent is selected from alcohol, ethanol, methanol, isopropanol, diethyl ether, N,N- dimethylformamide, tetrahydrofuran or water or mixture thereof. 10 13. The method as claimed in any one of the claims 1-2, wherein in step-d, i. the base if used, is selected from an alkali metal alkoxide or alkaline earth metal alkoxide; ii. the acid is selected from sulphuric acid, hydrochloric acid, or hydrobromic acid; and iii. the solvent is selected from alcohol, methanol, ethanol, tetrahydrofuran, 2- 15 methyltetrahydrofuran, acetonitrile, or N,N-dimethylformamide or water.

14. A method for the synthesis of a compound of formula (V) comprising the steps of: a-1. reacting a compound of formula (VI) with a halogenating agent selected from chlorine or bromine in the presence of an alcoholic solvent to obtain a compound of formula (Z);RY20 represent C1-C6-alkyl; or Rxand RYtogether with the atom to which they are attached may form a 5- or 6-membered ring and X represents Br or Cl; a-2. obtaining the compound of formula (V) by reacting the compound of formula (Z) with an acid;, wherein Rxand RY25 represent C1-C6-alkyl; or Rxand RYtogether with the atom to which they are attached may form a 5- or 6-membered ring and X represents Br or Cl.PI External 15. The method as claimed in claim 2 or claim 4, wherein said method further comprises the following step: A. preparing a compound of formula (VI) by i. acetylating a compound of Formula (VIII) with acetyl chloride or acetic anhydride in the 5 presence of a suitable catalyst and an optional solvent to obtain a compound of Formula (VII),ii. reacting the compound of Formula (VII) with a cyanide source in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (VI),10 .

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