An improved process for the preparation of fluopyram

Abstract

The present invention relates to an improved process for the preparation of benzamide compound. More particularly, the present invention relates to an improved process for the preparation of Fluopyram of Formula (VI).

Description

[0001] AN IMPROVED PROCESS FOR THE PREPARATION OF FLUOPYRAM

[0002] FIELD OF THE INVENTION

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

[0004] BACKGROUND OF THE INVENTION

[0005] Fluopyram belongs to a benzamide fungicide class of compounds containing two trifluoromethyl groups, chemically known as A-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl] ethyl }-2-(trifluoromethyl) benzamide. It is a new generation of SDHI (succinate dehydrogenase inhibitor) fungicide and nematicide.

[0006] Fluopyram acts on complex II on the mitochondrial respiratory electron transport chain, interfering with its respiratory action by inhibiting the activity of the target succinate dehydrogenase. It effectively controls several diseases including but not limited to botrytis, powdery mildew, Soybean sudden death syndrome (Fusarium virgulifarme) etc. It can be used for preventing and controlling several diseases on fruits and vegetables including but not limited to potato, sugar-beet, grapes, pear trees, cotton, soybean, strawberries, bananas, apples, cucumbers, tomatoes and the like and field crops, such as chilli, rice (paddy), onion, and is an efficient, green and low-toxicity fungicide.

[0007] It is not only part of new generation with excellent fungicidal properties, but also has nematicidal activity, a seed treatment agent, an agricultural product storage preservative, and has multiple functions. Fluopyram has following chemical structure -

[0008]

[0009] Further, PCT application WO0111965 discloses similar synthesis by reaction of 2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl] ethanamine with 2,6-Dichloro benzoyl chloride using triethylamine (TEA) as acid binding agent (represented by scheme- 1).

[0010] Scheme- 1

[0011]

[0012] Furthermore, PCT application W02006067103 discloses preparation of Fluopyram starting from 2-trifluoromethyl benzoic acid. The preparation trifluoromethyl benzamide from corresponding benzoyl chloride was carried out using aqueous ammonia, wherein, the yield of amide claimed was 85-87% and the trifluoromethyl benzamide obtained was then reacted with formaldehyde under alkaline conditions to obtain A-hydroxymcthyl 2- trifluoromethyl benzamide. A-hydroxymethyl 2- trifluoromethyl benzamide was further reacted with acetic anhydride to obtain A-acetoxymethyl derivative. In another step 2,3 dichlro-5-trifluoromethyl pyridine is reacted with diethyl malonate under alkaline condition to get malonic acid ethyl ester and is reacted with A-acetoxy-2-trifluoromethyl benzamide using sodium hydride in THF solvent (represented by scheme-2).

[0013] Scheme-2

[0014]

[0015] Thus, the process disclosed in the prior arts involves dangerous chemicals that are difficult to handle on commercial scale like sodium hydride Thus large-scale operation is poor and are not suitable for an efficient large scale commercial production and therefore, it makes the process economically troublesome. Further, due to multistep synthesis the equipment and energy cost will be much higher.

[0016] Therefore, it is desirable to provide more economical, less hazardous, easy and commercially feasible process for the production of benzamide compound,

[0017]

[0018] Fluopyram of Formula (VI).

[0019] Accordingly, there is an ongoing and long felt need for a process for preparing the Fluopyram of Formula (VI) with an improved yield, and purity. Thus, the inventor of the present invention by exhaustive research and development obtains a process for preparing Fluopyram of Formula (VI) which is simple, cost-effective and economical.

[0020] It is the objective of the present invention to provide a process for preparing Fluopyram of Formula (VI) under basic conditions in which the yield, purity and selectivity are improved, as a need still remains for simple, cost effective, consistently reproducible and environmentally friendly process for preparing highly pure, stable Fluopyram.

[0021] Therefore, the present invention provides an improved process for preparation of Fluopyram of Formula (VI) which overcomes the drawbacks of prior arts. Therefore, the present invention comprises a novel, inventive and industrially useful process for the preparation of Fluopyram of formula (VI).

[0022] The present invention satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior arts.

[0023] OBJECTIVE AND ADVANTAGES OF THE INVENTION

[0024] The main objective of the present invention is to provide a simple, economically advantageous and cost-effective process for the preparation of Fluopyram of Formula (VI), with high purity and yield of Fluopyram on a commercial scale.

[0025] Another objective of the present invention is to provide a novel process for the preparation of Fluopyram of Formula (VI), in free form or in agrochemically acceptable salt or in formulation form starting from readily accessible and economical intermediates which are easy to handle. Another objective of the present invention is to provide a novel and effective process for preparation of Fluopyram of formula (VI), with reduced or minimal waste generation.

[0026] Another objective of the present invention is to provide a process for the preparation of Fluopyram of Formula (VI), with minimized side reaction and / or formation of by-products. Another objective of the present invention is to provide a process for the preparation of Fluopyram of formula (VI), that involves less expensive and readily available reagents and solvents.

[0027] Another objective of the present invention is to provide a process for the preparation of Fluopyram of formula (VI), which is industrially and economically robust process with safe operations.

[0028] Another objective of the present invention is to provide a process for the preparation of Fluopyram of formula (VI), which results in improved yield and purity of the final product. Another objective of the present invention is to provide a process for the preparation of Fluopyram of formula (VI), wherein, less effluent is generated.

[0029] Another objective of the present invention is to provide a process for the preparation of Fluopyram of formula (VI), its intermediates and process of preparation of intermediates having an improved purity and yield.

[0030] Another objective of the present invention is to provide a process wherein, a cleaner product is obtained with minimum and / or no by-products formation.

[0031] Another objective of the present invention is to provide the process for the preparation of Fluopyram of formula (I), its intermediates and process of preparation of intermediates involving milder conditions like moderate temperature and pressure.

[0032] Another objective of the present invention is to provide a novel process for the preparation of Fluopyram in free form or in agro-chemically acceptable salt which can be further used for formulating into suitable dosage forms.

[0033] It is an objective of the present invention to provide an improved process for the preparation and manufacture of Fluopyram of formula (VI).

[0034] Yet another object of the present invention is to provide a process for the preparation and manufacture of Fluopyram of formula (VI), suitable for scale up on a commercial scale. Some or all these and other objects of the invention can be achieved by way of the invention described hereinafter.

[0035] Advantages of the present invention:

[0036] • The process, intermediates and process of preparation of intermediates of the present invention provides improved purity and yield.

[0037] • The process of the present invention provides easy work up methods.

[0038] • The process of the present invention is suitable for large scale operation.

[0039] • The process of the present invention involves the usage of less expensive and readily available reagents and solvents.

[0040] • The process of the present invention provides reduced usage of hazardous reagents. • Production method of the present invention is economically viable and operationally safe.

[0041] • The process of the present invention provides improved yield & purity of the final product (i.e., Fluopyram of Formula (VI)).

[0042] • The process of the present invention ensures reduced time and temperature conditions during the course of reaction.

[0043] SUMMARY OF THE INVENTION

[0044] Accordingly, the main aspect of the present invention is to provide an improved process for the preparation of Fluopyram of Formula (VI). Provided herein is simple, cost effective and consistently reproducible process for the preparation of highly pure and stable form of Fluopyram.

[0045] In an aspect, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), using cost effective and readily available reagents.

[0046] In another aspect, the present invention provides a process for the preparation of Fluopyram of Formula (VI), in simple manner and in good yield and purity.

[0047] In another aspect, the present invention provides a process for the preparation of Fluopyram of Formula (VI), its intermediates and process of preparation of intermediates involving milder conditions like moderate temperature and pressure.

[0048] In another aspect, the present invention provides an improved process for preparation and manufacture of Fluopyram of formula (VI).

[0049] In an aspect, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising: a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine in the presence of chlorinating agent and a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine;

[0050] b) reacting the compound of formula II with suitable cyanide selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, and a suitable solvent yields a compound of formula III, i.e., (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile which on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, i.e., 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine6yridine, and

[0051] c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a suitable base obtains a target compound, i.e., Fluopyram of Formula (VI).

[0052] In an aspect, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising:

[0053] a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine with V-Chloro succinimide (NCS) in the presence of a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine;

[0054] b) reacting the compound of formula II with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, yields a compound of formula III, i.e., (3-Chloro-5- trifluoromethyl-pyridin-2-yl)-acetonitrileyridine which on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, i.e., 2-(3-Chloro- 5-trifluoromethyl-pyridin-2-yl)-ethylamine; and

[0055] c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a base obtains a target compound, i.e., Fluopyram of Formula (VI).

[0056] In an aspect, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising:

[0057] a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine with V-Chloro succinimide (NCS) in the presence of a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine; b) reacting the compound of formula II with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, yields a compound of formula III, i.e., (3-Chloro-5- trifluoromethyl-pyridin-2-yl)-acetonitrile which on treatment with hydrogen in presence of Raney Ni as catalyst obtains desired amine of formula IV, i.e., 2-(3-Chloro- 5-trifluoromethyl-pyridin-2-yl)-ethylamine; and

[0058] c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a base such as TEA (Triethylamine) obtains a target compound, i.e., Fluopyram of Formula (VI).

[0059] The process of the present invention is represented by scheme 5 as below:

[0060] Scheme 5

[0061]

[0062] DETAILED DESCRIPTION OF THE INVENTION

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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:

[0067] 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.

[0068] 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.

[0069] 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.

[0070] In an embodiment, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising:

[0071] a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine in the presence of chlorinating agent and a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine;

[0072] b) reacting the compound of formula II with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, and a suitable solvent yields a compound of formula III, i.e., (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile which on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, i.e., 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine; and

[0073] c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a suitable base obtains a target compound, i.e., Fluopyram of Formula (VI).

[0074] According to further embodiment, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising:

[0075] a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine with A-Chloro succinimide (NCS) in the presence of a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine;

[0076] b) reacting the compound of formula II with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, yields a compound of formula III, i.e., (3-Chloro-5- trifluoromethyl-pyridin-2-yl)-acetonitrile which on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, i.e., 2-(3-Chloro- 5-trifluoromethyl-pyridin-2-yl)-ethylamine; and

[0077] c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a suitable base obtains a target compound, i.e., Fluopyram of Formula (VI).

[0078] In yet another embodiment, the present invention provides an improved process for the preparation of Fluopyram of Formula (VI), comprising:

[0079] a) chlorinating a compound of formula I, i.e., 3-Chloro-2-methyl-5- trifluoromethylpyridine with A-Chloro succinimide (NCS) in the presence of a suitable solvent, to obtain a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5- trifluoromethy Ipyridine;

[0080] b) reacting the compound of formula II with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, yields a compound of formula III, i.e., (3-Chloro-5- trifluoromethyl-pyridin-2-yl)-acetonitrile which on treatment with hydrogen in presence of Raney Ni as suitable catalyst obtains desired amine of formula IV, i.e., 2- (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine; and c) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a suitable base such as TEA (Triethylamine) obtains a target compound, i.e., Fluopyram of Formula (VI).

[0081] According to the embodiments of the present invention, the present invention relates to an improved process for the preparation, synthesis and manufacture of Fluopyram of formula (VI).

[0082] According to the embodiments, the present invention provides a simple and cost-effective process for the preparation and manufacture of Fluopyram of formula (VI).

[0083] According to the embodiments, the present invention provides an improved process for preparation and manufacture of Fluopyram of formula (VI), using less expensive and readily available reagents.

[0084] According to an embodiment, the present invention provides an improved process of preparation of Fluopyram (VI), which comprises reaction of a compound of formula I, i.e., 3-Chloro-2-methyl-5-trifluoromethylpyridine, with A-Chloro succinimide (NCS) to give a compound of formula II, i.e., 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine;

[0085]

[0086] The compound of formula II on further reaction with suitable cyanides selected from but not limited to sodium cyanide, potassium cyanide, copper cyanide, acetone cyanohydrin, potassium ferrocyanide, yields a compound of formula III, i.e., (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile;

[0087]

[0088] The compound of formula III, is then on treatment with hydrogen in presence of Raney Ni as catalyst yields a desired amine of formula IV z.e., 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine;

[0089]

[0090] Finally, the compound of formula IV is reacted with substituted benzoyl chloride of formula (V) z.e., 2-(trifluoromethyl) benzoylchloride in the presence of suitable base, obtains a target compound of Formula VI, i.e., A-{2-[3-chloro-5-(trifluoromethyl) pyridin-2-yl] ethyl}-2-(trifluoromethyl)benzamide or Fluopyram.

[0091] Accordingly, the improved process of the present invention provides a yield of above 96% of Fluopyram of formula (VI), and purity above 98%.

[0092] According to the embodiments of the present invention, the suitable solvent for example includes but are not limited to polar solvent is selected from the group comprising dichloromethane, ethylene dichloride (EDC), acetonitrile, tetrahydrofuran, tert-butanol, isopropanol (IPA), methanol, ethanol, acetic acid, A, Ar-dimethylformamide (DMF), 1,4-di oxane, diethyl ether, ethyl acetate, acetone, dimethylsulfoxide (DMSO) or combination thereof

[0093] In one of the embodiments, the base is selected from an organic base or inorganic base, or combination thereof.

[0094] In one of the embodiments, the organic base can be selected from the group comprising 4-dimethylaminopyridine (DMAP), diisopropylamine, diisopropylethylamine, triethylamine (TEA), dimethylamine, trimethyl amine, pyridine, A- methyl morpholine, 3 -picoline, 2-picoline, 4-picoline, or combination thereof.

[0095] In one of the embodiments, the inorganic base can be selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, calcium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate or combination thereof. In the embodiments of the present invention, the chlorinating agent is selected from the group including but not limited to iV-chloro succinimide (NCS), thionyl chloride, phosphorus pentachloride (PC15), phosphorus trichloride (PC13), Tosyl-chloramide, hydrochloric acid, N-chloro compounds, sodium hypochlorite, sulfuryl chloride etc or combination thereof.

[0096] In one of the embodiments, the suitable catalyst used for increasing the speed of the reaction is selected from Raney Nickel catalyst, Iron catalyst, Copper catalyst, Zinc catalyst, Palladium on carbon (Pd / C), Platinum on carbon (Pt–C) Cobalt Catalyst, ammonium formate, sodium formate, tetrabutylammonium bromide, metal iodides including but not limited to Cuprous iodide, Potassium iodide, etc or combination thereof.

[0097] In the embodiments of the present invention, the suitable cyanide compounds are selected from the group comprising of but not limited to metal cyanides such as sodium cyanide, potassium cyanide, copper cyanide, or acetone cyanohydrin, potassium ferrocyanide or combination thereof.

[0098] In an embodiment of the present invention, process for preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II), comprises- A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer charged with suitable solvent followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I). The mixture was stirred for 20-40 mins. Suitable chlorinating agent was added portion-wise. The reaction mass was slowly warmed to 50-65°C and then refluxed. The reaction progress was monitored by TLC and HPLC. After completion, and the reaction mass was filtered. The residue was washed with suitable solvent. The combined organic layer was washed with water, brine and dried over anhydrous sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): upto 97%, Yield upto 89% were achieved.

[0099] In another embodiment of present invention, the process for preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II), comprises- A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I). The mixture was stirred for about 20-40 mins. Chlorinating agent was added portion-wise. The reaction mass was slowly warmed to 50 °C -65 °C and then heated to higher temperature above 80° C. The reaction progress was monitored by TLC and HPLC. After completion, suitable solvent was removed under reduced pressure. To the residue thus obtained, another suitable solvent was added and filtered. The residue was washed with solvent. The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area) was found about 95%, and yield above 80%.

[0100] In another embodiment of the present invention, the process for preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II), comprises- A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) and a radical initiator including but not limited to peroxides, such as benzoyl peroxide. The mixture was stirred for 20-40 mins. Chlorinating agent was added portion-wise. The reaction mass was slowly warmed to 50 °C - 70°C and then refluxed. The reaction progress was monitored by TLC and HPLC. After completion, solvent was removed under reduced pressure. The residue was diluted with ice cold water and extracted with suitable solvent. The combined organic layer was washed with water, brine and dried over anhydrous sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): was found to be above 95%, Yield: above 75%.

[0101] According to the embodiments of the present invention, after the purification, Formula II was obtained with HPLC purity up to 97.3%, and yield up to 89%.

[0102] In an embodiment of the present invention, process of preparation of (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III), comprises- A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent followed by Tetrabutylammonium Bromide, A, A'-Dimethylethylenediamine, and suitable catalysts including but not limited to metal iodide including but not limited to cuprous or potassium iodide or combinations thereof, suitable cyanide compounds including but not limited to metal cyanides such as sodium cyanide, potassium cyanide, copper cyanide, or acetone cyanohydrin, potassium ferrocyanide or combination thereof. The mixture was stirred for 20-40 mins. 3-Chloro-2-chloromethyl-5- trifluoromethylpyridine (Formula II) was added in four equal lots. The next lot was added only after the complete consumption of the previous lot. The reaction was conducted at high temperature of about 95-135° C. The reaction progress was monitored by TLC and HPLC. After completion, the reaction mass is cooled to 45-70° C. Solvent was removed under reduced pressure by process of downward distillation. To the residue thus obtained was poured on crushed ice. The product was extracted using suitable solvent. The combined organic layer was washed with water, brine and dried over anhydrous sodium sulfate, filtered, concentrated to furnish (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). After purification, HPLC purity (area): above 95%, Yield above upto 93% was observed. The aqueous layer was treated with aqueous sodium hypochlorite solution. All the glassware used for the reaction and work up were also properly washed with aqueous sodium hypochlorite solution to ensure safe disposal and elimination of malodorous, or reactive residues. Use of sodium hypochlorite thus serves both as a quenching and decontamination step, improving process safety and environmental compliance.

[0103] In another embodiment of the present invention, process of preparation of (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III), comprises use of suitable solvent followed by phase transfer catalyst, such as but not limited to Tetrabutylammonium Bromide, ligand such as but not limited to 1,10-phenanthroline, metal iodide including but not limited to cuprous or potassium iodide or combinations thereof, suitable cyanide compounds including but not limited to metal cyanides such as sodium cyanide, potassium cyanide, copper cyanide, or acetone cyanohydrin, potassium ferrocyanide or combination thereof or combination thereof. The mixture was stirred for abour 20-40 mins. 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II) was added in four equal lots. The next lot was added only after the complete consumption of the previous lot. The reaction was refluxed. The reaction progress was monitored by TLC and HPLC. After completion, the reaction mass was cooled to 50 to 65° C. Suitable solvent such as Acetonitrile was removed under reduced pressure by downward distillation. The residue thus obtained was poured on crushed ice. The product was extracted using another suitable solvent, such as but not limited to ethylene dichloride (EDC). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). After purification, HPLC purity (area): was found to be above 96%, Yield: was found to be above 72%. The aqueous layer was treated with aqueous sodium hypochlorite solution. All the glassware used for the reaction and work up were also properly washed with aqueous sodium hypochlorite solution. According to the embodiments of the present invention, after the purification, Formula III was obtained with HPLC purity up to 96.2%, and yield up to 93%.

[0104] In an embodiment of the present invention, the preparation of 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) comprises different methods-i. Method A

[0105] Suitable solvent such as Isopropanol (IPA) was charged to stainless steel (SS) pressure reactor followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). Suitable catalyst including but not limited to Raney-Nickel was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with Hydrogen. After the cycles, Hydrogen was filled in the reactor till the pressure reached around 5-8 Bar. The reaction temperature was taken to 80-100° C. The reaction progress was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake obtained, was washed with suitable solvent such as isopropanol. The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area): was found to be above 97%, Yield was found to be above 89 %.

[0106] ii. Method B

[0107] Suitable solvents such as Isopropanol was charged to SS pressure reactor followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). Catalyst including but not limited to Pd-C was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with hydrogen. After the cycles, hydrogen was filled in the reactor till the pressure reached 4-6 Bar. The reaction temperature was taken to 80-100° C. The reaction progress was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake was washed with suitable solvent such as isopropanol. The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area) was found to be above 97%, Yield about 92 %. iii. Method C

[0108] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent such as but not limited to Isopropanol (IPA) followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). Suitable catalyst such as but not limited to Raney-nickel was added carefully. The mixture was stirred for 30 mins. Formate compounds including but not limited to ammonium formate or sodium formate was added. The reaction was conducted at reflux. The reaction progress was monitored by TLC and HPLC. After completion, the solvent was removed under reduced pressure. The residue thus obtained was treated with crushed ice. The product was extracted using suitable solvent such as but not limited to ethylene dichloride (EDC). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area) was found to be above 95%, Yield was found to be above 85%.

[0109] iv. Method D

[0110] Suitable solvent such as Isopropanol was charged to SS pressure reactor followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). Suitable catalyst Pt-C (1.27 g) was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with hydrogen. After the cycles, hydrogen was filled in the reactor till the pressure reached around 6-8 Bar. The reaction temperature was taken to 80-100° C. The reaction progress was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake was washed with suitable solvent such as but not limited to isopropanol. The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area) was found to be above 97%, Yield was found to be above 95 %.

[0111] According to the embodiments of the present invention, after the purification, Formula IV was obtained with HPLC purity up to 97.8%, and yield up to 95%.

[0112] In an embodiment of the present invention, the process for preparation of N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Fluopyram) (Formula VI) comprises different methods-i. Method A

[0113] A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent such as but not limited to ethylene dichloride followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) and base such as triethyl amine (TEA). The mixture was stirred for 20-40 mins. The reaction mass was cooled to about 0-15° C. 2-Trifluoromethyl-benzoyl chloride (Formula V) in suitable solvent such as EDC was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above the certain temperature limit. After complete addition, the reaction mass was stirred at room temperature. The reaction progress was monitored by TLC and HPLC. After completion, water was added. Organic layer was separated. The aqueous layer was washed with suitable solvent such as but not limited to ethylene dichloride (EDC). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish A-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Formula VI). After purification, HPLC purity (area) was found to be above 98%, Yield: above 95%.

[0114] ii. Method B

[0115] A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent such as but not limited to ethylene dichloride (EDC) followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) and suitable organic base such as but not limited to Diisopropylethylamine. The mixture was stirred for 20-40 mins. The reaction mass was cooled to 0-15°C. 2-Trifluoromethyl-benzoyl chloride (Formula V) in suitable solvent such as ethylene dichloride (EDC) was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above a certain temperature limit. After complete addition, the reaction mass was stirred at room temperature. The reaction progress was monitored by TLC and HPLC. After completion, water was added. Organic layer was separated. The aqueous layer was washed with suitable solvent such as but not limited to ethylene dichloride (EDC). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish A-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Formula VI). After purification, HPLC purity (area) was found to be above 97%, Yield: was found to be above 95%.

[0116] iii. Method C comprises - A four necked glass reactor fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with suitable solvent such as ethylene dichloride (EDC) followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) and suitable inorganic base including but not limited to Potassium carbonate. The mixture was stirred for 20-40 mins. The reaction mass was cooled to around 0-15° C. 2-Trifluoromethyl-benzoyl chloride (Formula V) in suitable solvent such as ethylene dichloride (EDC) was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above a certain temperature limit. After complete addition, the reaction mass was stirred at room temperature. The reaction progress was monitored by TLC and HPLC. After completion, the reaction mass was filtered and the solid cake was washed twice with suitable solvent such as EDC. The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish A-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl] ethyl] -2-(trifluoromethyl)benzamide (Formula VI). After purification, HPLC purity (area): was found to be above 98%, Yield: was found to be about 97%.

[0117] According to the embodiments of the present invention, after the purification, Fluopyram (Formula VI) was obtained with HPLC purity up to 98.7%, and yield up to 97%.

[0118] According to the embodiments of the present invention, the reaction is carried at a temperature of range from 0°C to 140°C.

[0119] According to the embodiments of the present invention, the reaction is carried out at a range of pressure from an atmospheric pressure up to 10 bar.

[0120] The process for preparing fluopyram of formula (I) according to the present invention gave fluopyram with purity of 95% to 99% and a yield of about 95 to 97 %.

[0121] According to another embodiment, the present invention also provides an agrochemical composition, wherein the composition comprises at least a bio-active effective amount of Fluopyram of formula (VI).

[0122] According to another embodiment, the present invention also provides an agrochemical composition wherein the composition further comprises one or more agrochemically acceptable excipients.

[0123] According to another embodiment, the present invention also provides a process for preparing the agrochemical composition comprising Fluopyram of formula (VI).

[0124] It is to be understood that the description of the present invention has been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known.

[0125] EXAMPLES

[0126] Although the content of the present invention is further specifically explained using examples, the present invention is not limited to the following examples as long as the gist of the present invention is not exceeded. The following examples are presented to further explain the invention with experimental conditions, which are purely illustrative and are not intended to limit the scope of the invention.

[0127] For the purpose of clarity and as an aid in the understanding of the invention, as disclosed and claimed herein, the following terms and abbreviations are defined below:

[0128] Formula I: 3-Chloro-2-methyl-5-trifluoromethylpyridine;

[0129] Formula II: 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine;

[0130] Formula III: (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile;

[0131] Formula IV: 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine;

[0132] Formula V: 2-(trifluoromethyl) benzoylchloride;

[0133] Formula VI: Fluopyram or (N-{2-[3-chloro-5-(trifluoromethyl) pyridin-2-yl] ethyl}-2-(trifluoromethy l)benzamide).

[0134] The improved process of the present invention for the preparation of compound of Formula VI, is represented stepwise in scheme provided below:

[0135]

[0136] SCHEME 5

[0137] The present invention provides an improved process for the preparation of Fluopyram of Formula (VI), which comprises chlorination of compound of formula I, z.e., 3-Chloro-2-methyl-5-trifluoromethylpyridine in the presence of chlorinating agent and suitable solvent, to obtain a compound of formula II, z.e., 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine; Then reacting the compound of formula II with suitable cyanide compounds including but not limited to metal cyanides such as sodium cyanide, potassium cyanide, copper cyanide, or acetone cyanohydrin, potassium ferrocyanide, and suitable solvent which yields a compound of formula III, z.e., (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile. Compound of formula III on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, z.e., 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine. Reacting the compound of formula IV with substituted benzoyl chloride in the presence of base obtains a target compound, i.e., Fluopyram of formula VI.

[0138] According to another embodiment, there is provided a process for preparing agrochemical composition comprising highly pure and stable fluopyram obtained as per the process disclosed herein. Yet in another embodiment, agrochemical compositions comprise at least a bio-active effective amount of highly pure and stable fluopyram obtained by the processes disclosed herein. The agrochemical compositions further contain one or more agrochemically acceptable excipients. Suitable excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and consideration of standard procedures and reference works in the field.

[0139] 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.

[0140] 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.

[0141] Example 1: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)-i. Method A

[0142] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Acetonitrile (375 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (113.4 g). The mixture was stirred for 30 mins. N- Chlorosuccinimide (NCS) (109.8 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, acetonitrile was removed under reduced pressure. To the residue thus obtained, ethylene dichloride (EDC) (400 mL) was added and filtered. The residue was washed with ethylene dichloride (EDC). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): 96.4%, Yield: 110 g, 85%.

[0143] Example 2: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method B

[0144] A four necked glass reactor (2 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with ethylene dichloride (EDC) (450 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (154.7 g). The mixture was stirred for 30 mins. N-Chloro succinimide (NCS) (109.8 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, the reaction mass was filtered. The residue was washed with ethylene dichloride EDC. The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (II). After purification, HPLC purity (area): 97.3%, Yield: 157 g, 89%.

[0145] Example 3: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method C

[0146] A four necked glass reactor (0.5 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with N,N-Dimethylformamide (DMF) (130 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (67 g). The mixture was stirred for 30 mins. N-Chlorosuccinimide (NCS) (47.6 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then heated to 85-90° C. The reaction was monitored by TLC and HPLC. After completion, DMF was removed under reduced pressure. To the residue thus obtained, ethylene dichloride (EDC) (250 mL) was added and filtered. The residue was washed with EDC. The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): 95%, Yield: 61.9 g, 81%. Example 4: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method D

[0147] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Acetonitrile (175 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (77.3 g) and benzoyl peroxide (4.1 g). The mixture was stirred for 30 mins. Phosphorous trichloride (PCl3) (59.1 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, acetonitrile was removed under reduced pressure. The residue was diluted with ice cold water (200 g) and extracted with ethylene chloride (2 X 150 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (II). After purification, HPLC purity (area): 96%, Yield: 67 g, 76%.

[0148] Example 5: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method E

[0149] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with N,N-dimethylformamide (DMF) (130 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (67 g) and benzoyl peroxide (4.1 g). The mixture was stirred for 30 mins. Phosphorous trichloride (PCl3) (51.3 g) was added portion- wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, DMF was removed under reduced pressure. The residue was diluted with ice cold water (200 g) and extracted with ethylene chloride (2 X 150 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): 96.4%, Yield: 60.4 g, 79%.

[0150] Example 6: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method F

[0151] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Acetonitrile (145 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I) (56.7 g) and benzoyl peroxide (3.5 g). The mixture was stirred for 30 mins. Phosphorous pentachloride (PCl5) (65.7 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, acetonitrile was removed under reduced pressure. The residue was diluted with ice cold water (200 g) and extracted with ethylene chloride (2 X 150 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): 93.4%, Yield: 47.2 g, 73%.

[0152] Example 7: Preparation of 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II)- Method G

[0153] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with N,N-dimethylformamide DMF (125 mL) followed by 3-Chloro-2-methyl-5-trifluoromethylpyridine (Formula I)(46.4 g) and benzoyl peroxide (2.9 g). The mixture was stirred for 30 mins. Phosphorous pentachloride (PCl5) (53.8 g) was added portion-wise. The reaction mass was slowly warmed to 55 °C - 60 °C and then refluxed. The reaction was monitored by TLC and HPLC. After completion, N,N-dimethylformamide (DMF) was removed under reduced pressure. The residue was diluted with ice cold water (200 g) and extracted with ethylene chloride (2 X 150 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II). After purification, HPLC purity (area): 94.7%, Yield: 38.2 g, 72%.

[0154] Example 8: Preparation of (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III)- Method A

[0155] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with N,N-Dimethylformamide (DMF) (250 mL) followed by Tetrabutylammonium Bromide (1.6 g), N,N'-Dimethylethylenediamine (10 mol %), Cuprous iodide (10 mol%), Potassium iodide (20 mol%), Cuprous cyanide (1 m / m) and sodium cyanide (82.8 g). The mixture was stirred for 30 mins. 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II) (112.3 g) was added in four equal lots. The next lot was added only after the complete consumption of the previous lot. The reaction was conducted at 115-120° C. The reaction was monitored by TLC and HPLC. After completion, the reaction mass is cooled to 55-60° C. DMF was removed under reduced pressure by downward distillation. To the residue thus obtained was poured on crushed ice. The product was extracted using ethylene dichloride (EDC) (2 X 250 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). After purification, HPLC purity (area): 95.6%, Yield: 98.2 g, 93%. The aqueous layer was treated with aqueous sodium hypochlorite solution. All the glassware used for the reaction and work up were also properly washed with aqueous sodium hypochlorite solution. This ensures safe disposal and elimination of malodorous, or reactive residues. Use of sodium hypochlorite thus serves both as a quenching and decontamination step, improving process safety and environmental compliance.

[0156] Example 9: Preparation of (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III)-Method B

[0157] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Acetonitrile (ACN) (400 mL) followed by Tetrabutylammonium Bromide (0.7 g), 1,10-phenanthroline (10 mol %), Potassium iodide (20 mol%), Cuprous cyanide (1 m / m) and sodium cyanide (71.5 g). The mixture was stirred for 30 mins. 3-Chloro-2-chloromethyl-5-trifluoromethylpyridine (Formula II) (96.9 g) was added in four equal lots. The next lot was added only after the complete consumption of the previous lot. The reaction was refluxed. The reaction was monitored by TLC and HPLC. After completion, the reaction mass is cooled to 55-60° C. Acetonitrile was removed under reduced pressure by downward distillation. The residue thus obtained was poured on crushed ice. The product was extracted using ethylene dichloride (EDC) (2 X 250 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III).

[0158] After purification, HPLC purity (area): 96.2%, Yield: 66.5 g, 73%. The aqueous layer was treated with aqueous sodium hypochlorite solution. All the glassware used for the reaction and work up were also properly washed with aqueous sodium hypochlorite solution.

[0159] Example 10: Preparation of (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III)-Method C

[0160] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Dimethylsulfoxide (DMSO) (100 mL) followed by Tetrabutylammonium Bromide (0.2 g), N,N'-Dimethylethylenediamine (10 mol %), Cuprous iodide (10 mol%), Potassium iodide (20 mol%), Cuprous cyanide (1 m / m) and sodium cyanide (22.6 g). The mixture was stirred for 30 mins. 3-Chloro-2-chloromethyl-5- trifluoromethylpyridine (Formula II) (30.6 g) was added in four equal lots. The next lot was added only after the complete consumption of the previous lot. The reaction was conducted at 100-105° C. The reaction was monitored by TLC and HPLC. After completion, the reaction mass was cooled to room temperature and was poured on crushed ice. The product was extracted using ethylene dichloride (EDC) (2 X 250 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III). After purification, HPLC purity (area): 95.7%, Yield: 20.7 g, 72%. The aqueous layer was treated with aqueous sodium hypochlorite solution. All the glassware used for the reaction and work up were also properly washed with aqueous sodium hypochlorite solution.

[0161] Example 11: Preparation of 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV)-Method A

[0162] Isopropanol (500 mL) was charged to SS pressure reactor (2 Lit) followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III) (115.8 g). Raney-Nickel (10 g) was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with Hydrogen. After the cycles, Hydrogen was filled in the reactor till the pressure reached 6 Bar. The reaction temperature was taken to 90° C. The reaction was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake obtained, was washed with isopropanol (2 X 75 mL). The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area): 97.6%, Yield: 99.7 g, 89 %.

[0163] Example 12: Preparation of 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV)-Method B

[0164] Isopropanol (500 mL) was charged to SS pressure reactor (2 Lit) followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III) (94.7 g). Catalyst such as Pd-C (2.2 g) was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with Hydrogen. After the cycles, Hydrogen was filled in the reactor till the pressure reached 5 Bar. The reaction temperature was taken to 90° C. The reaction was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake was washed with isopropanol (2 X 75 mL). The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area): 97.8%, Yield: 84.31 g, 92 %.

[0165] Example 13: Preparation of 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV)-Method C

[0166] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with Isopropanol (IPA) (500 mL) followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III) (80 g). Raney-nickel (2.1 g) was added carefully. The mixture was stirred for 30 mins. Ammonium formate (95.3 g) was added. The reaction was conducted at reflux. The reaction was monitored by TLC and HPLC. After completion, the solvent was removed under reduced pressure. The residue thus obtained was treated with crushed ice. The product was extracted using ethylene dichloride (EDC) (3 X 250 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area): 95.7%, Yield: 66.5 g, 86%.

[0167] Example 14: Preparation of 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV)-Method D

[0168] Isopropanol (500 mL) was charged to SS pressure reactor (2 Lit) followed by (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-acetonitrile (Formula III) (94.7 g). Pt-C (1.27 g) was added very carefully. The reactor was sealed. The reactor was subjected to three vacuum-fill cycles with Hydrogen. After the cycles, Hydrogen was filled in the reactor till the pressure reached 7 Bar. The reaction temperature was taken to 90° C. The reaction was monitored by withdrawing the sample from the reactor by TLC and HPLC. After completion, the reaction mass was filtered using filtration aid. The solid cake was washed with isopropanol (2 X 75 mL). The combined isopropanol layer was concentrated under vacuum to furnish crude 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV). After purification, HPLC purity (area): 97.8%, Yield: 87 g, 95 %.

[0169] Example 15: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Fluopyram) (Formula VI)- Method A

[0170] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with ethylene dichloride (250 mL) followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) (50 g) and triethyl amine (TEA) (65.6 g). The mixture was stirred for 30 mins. The reaction mass was cooled to 5-10° C. 2-Trifluoromethyl-benzoyl chloride (Formula V) (52.1 g) in EDC (100 mL) was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above 10° C. After complete addition, the reaction mass was stirred at room temperature. The reaction was monitored by TLC and HPLC. After completion, water (200 g) was added. Organic layer was separated. The aqueous layer was washed with ethylene dichloride (EDC) (2 X 50 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish A-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Formula VI). After purification, HPLC purity (area): 98.7%, Yield: 84.8 g, 96%.

[0171] Example 16: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Fluopyram) (Formula VI)- Method B

[0172] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with ethylene dichloride (EDC) (200 mL) followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) (45 g) and Diisoproylethylamine (75.6 g). The mixture was stirred for 30 mins. The reaction mass was cooled to 5-10° C. 2-Trifluoromethyl-benzoyl chloride (Formula V) (46.7 g) in ethylene dichloride (EDC) (100 mL) was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above 10° C. After complete addition, the reaction mass was stirred at room temperature. The reaction was monitored by TLC and HPLC. After completion, water (200 g) was added. Organic layer was separated. The aqueous layer was washed with ethylene dichloride (EDC) (2 X 50 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Formula VI).

[0173] After purification, HPLC purity (area): 97.7%, Yield: 75.9 g, 95.5%.

[0174] Example 17: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Fluopyram) (Formula VI)- Method C

[0175] A four necked glass reactor (1 Lit) fitted with condenser, thermometer pocket, thermometer, mechanical stirrer was charged with ethylene dichloride (EDC) (250 mL) followed by 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine (Formula IV) (43 g) and Potassium carbonate (71.7 g). The mixture was stirred for 30 mins. The reaction mass was cooled to 5-10° C. 2-Trifluoromethyl-benzoyl chloride (Formula V) (41.7 g) in ethylene dichloride (EDC) (75 mL) was added dropwise with deep-pipe in a such way that the reaction mass temperature should not rise above 10° C. After complete addition, the reaction mass was stirred at room temperature. The reaction was monitored by TLC and HPLC. After completion, the reaction mass was filtered and the solid cake was washed twice with EDC (2 X 50 mL). The combined organic layer was washed with water, brine and dried over anhydrous Sodium sulfate, filtered, concentrated to furnish N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-(trifluoromethyl)benzamide (Formula VI). After purification, HPLC purity (area): 98.2%, Yield: 68.5 g, 97%.

[0176] The present invention is more specifically explained by examples given above.

[0177] 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

We Claim:

1. An improved process for preparation of Fluopyram of Formula (VI), which comprises: a) Chlorinating a compound of formula I, i.e., 3-chloro-2-methyl-5- trifluoromethylpyridine in the presence of chlorinating agent and a suitable solvent, to obtain a compound of formula II, i.e., 3-chloro-2-chloromethyl-5-trifluoromethyl pyridine;b) reacting the compound of formula II with suitable cyanide compounds, and a suitable solvent to obtain a compound of formula III, i.e., (3-chloro-5-trifluoromethyl-pyridin- 2-yl] acetonitrile which on treatment with hydrogen in presence of a suitable catalyst obtains a desired amine of formula IV, i.e., 2-(3-chloro-5-trifluoromethyl-pyridin-2- yl)-ethylamine, andc) reacting the compound of formula IV with substituted benzoyl chloride in the presence of a suitable base obtains a final compound of Formula (VI) i.e Fluopyram.

2. The improved process as claimed in claim 1, wherein the chlorinating agent is selected from the group comprising of N-chloro succinimide (NCS), thionyl chloride, phosphorus pentachloride (PC15), phosphorus trichloride (PC13), Tosyl-chloramide, hydrochloric acid, N-chloro compounds, sodium hypochlorite, sulfuryl chloride or combination thereof.

3. The improved process as claimed in claim 1, wherein suitable solvent is selected from polar solvents selected from the group comprising of dichloromethane, ethylene dichloride (EDC), acetonitrile, tetrahydrofuran, tert-butanol, isopropanol (IP A), Methanol, ethanol, acetic acid, N,N-dimethylformamide (DMF), 1,4-dioxane, diethyl ether, ethyl acetate, acetone, dimethylsulfoxide (DMSO) or combination thereof.

4. The improved process as claimed in claim 1, wherein base can be selected from organic or inorganic base or a combination thereof.

5. The improved process as claimed in claim 4, wherein organic base is selected from the group comprising of 4-dimethylaminopyridine (DMAP), diisopropylamine, diisopropylethylamine, triethylamine (TEA), dimethylamine, trimethyl amine, pyridine, N- methylmorpholine, 3 -picoline, 2-picoline, 4-picoline, or combination thereof.

6. The improved process as claimed in claim 4, wherein inorganic base is selected from the group comprising of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, calcium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate or combination thereof.

7. The improved process as claimed in claim 1, wherein the suitable cyanide is selected from the group comprising of metal cyanide such as sodium cyanide, potassium cyanide, copper cyanide, potassium ferrocyanide, or acetone cyanohydrin, or a combination thereof.

8. The improved process as claimed in claim 1, wherein the suitable catalyst is selected from Raney Nickel catalyst, Iron catalyst, Copper catalyst, Zinc catalyst, Palladium on carbon (Pd / C), Platinum on carbon (Pt–C) Cobalt Catalyst, ammonium formate, sodium formate, Tetrabutylammonium Bromide, metal iodides selected from Cuprous iodide, Potassium iodide, or combination thereof.

9. The improved process as claimed in claim 1, wherein the reaction is carried at a temperature of range from 0°C to 140°C.

10. The improved process as claimed in claim 1, wherein the reaction is carried out at a range of pressure from an atmospheric pressure up to 10 bar.

11. The improved process as claimed in claim 1, wherein the yield of Fluopyram of Formula (VI) is in the range of 95% to 97% with purity of 95% to 99%.

12. An agrochemical composition, wherein the composition comprises at least a bio-active effective amount of Fluopyram of formula (VI) as obtained by the process claimed in claims 1-11.

13. The agrochemical composition as claimed in claim 12, wherein the composition further comprises one or more agrochemically acceptable excipients.

14. A process for preparing the agrochemical composition comprising Fluopyram of formula (VI) as claimed in claims 12-13.

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