PREPARATION OF FLECAINIDE AND ITS SALTS
TECHNICAL FIELD
The present application relates to a process for the preparation of flecainide and its salts.
BACKGROUND
Chemically flecainide acetate is benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-monoacetate (hereinafter referred to by its adopted name "flecainide acetate") and is structurally represented by Formula I.

Flecainide acetate is a class Ic antiarrhythmic agent used to prevent and treat tachyarrhythmias (abnormal fast rhythms of the heart). It is used to treat a variety of cardiac arrhythmias including paroxysmal atrial fibrillation (episodic irregular heartbeat originating in the upper chamber of the heart), paroxysmal supraventricular tachycardia (episodic rapid but regular heartbeat originating in the atrium), and ventricular tachycardia (rapid rhythms of the lower chambers of the heart). Flecainide works by regulating the flow of sodium in the heart, causing prolongation of the cardiac action potential.
Flecainide acetate is marketed as TAMBOCOR™ tablets in the dosage strengths of 50, 100 and 150 mg for oral administration.
U.S. Patent No. 3,900,481 disclose flecainide, its related compounds along with their pharmaceutically acceptable salts, pharmaceutical compositions and method of treatment. It also discloses preparation of flecainide that includes reaction of 2,5-

bis(2,2,2-trifluoroethoxy) benzoic acid derivatives with 2-aminometliylpyridine and the reduction of the pyridinebenzamide derivative.
U.S. Patent No. 4,684,733 describes a process for the preparation of flecainide which involves the conversion of 2,5-bis(2,2,2-trifluoroethoxy) benzoic acid into its acid chloride followed by reaction either with 2-(aminomethyl) piperidine to form flecainide in one step, or with 2-(aminomethyl)pyridine, followed by catalytic hydrogenation of the pyridine ring in two steps. Disadvantage of the one-step process is that the acid chloride reacts non-selectively with both nitrogen atoms of the 2-(aminomethyl) piperidine, resulting in a mixture of the two acylated isomers.
Different processes for the preparation of flecainide and its pharmaceutically acceptable salts are also disclosed in US 4,675,448, US 6,458,957, US 6,288,271, US 6,599,922, US 6,849,762, US 20040220409 A1 and US 20050059825 A1.
Accordingly, it is observed that there is a continuing need to develop improved process for producing flecainide and its pharmaceuticaly acceptable salts in safer and less expensive ways suitable for commercial manufacturing.
SUMMARY OF THE INVENTION
The present application relates to a process for the preparation of flecainide and its salts.
In one aspect the present application provides a process for the preparation of flecainide and its salts which process includes:
i) reacting 2,5-Bis(2,2,2-trifiuoro ethoxy) benzoic acid compound of Formula V with a chlorinating agent in an organic solvent;


ii) reacting the corresponding acid chloride intermediate obtained in step i) with 2-Amino methyl pyridine compound of Formula IV to afford 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide compound of Formula III; and

iii) reducing 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide compound of Formula III with palladium on a support carrier to afford the compound 2,5-Bis(2,2,2-trifluoro ethoxy)-N-(2-piperidylmethyl)benzamide (herein after referred to as "flecainide") of Formula II.

In another aspect the present application provides a process for the preparation of flecainide acetate by reacting flecainide of Formula II with acetic acid in toluene to afford flecainide acetate of Formula I.
Optionally, the flecainide obtained in step iii) can be converted into its pharmaceutically acceptable salts, in particular flecainide acetate.

In yet another aspect, the present invention provides pharmaceutical formulations comprising flecainide acetate of Formula I, produced by the process of the present invention, together with at least one pharmaceutically acceptable excipient.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a schematic representation of the process for preparing flecainide acetate of Formula I.
Fig. 2 is an illustrative X-ray powder diffraction pattern of crystalline form of flecainide of Formula II prepared in accordance with Example 2.
Fig. 3 is an illustrative X-ray powder diffraction pattern of crystalline form of flecainide acetate of Formula I prepared in accordance with Example 3.
DETAILED DESCRIPTION OF THE INVENTION
The present application relates to a process for the preparation of flecainide and its salts.
In one aspect the present application provides a process for the preparation of flecainide and its salts which process includes:
i) reacting 2,5-Bis(2,2,2-trifluoro ethoxy) benzoic acid compound of Formula V with a chlorinating agent in an organic solvent;

ii) reacting the corresponding acid chloride intermediate obtained in step i) with 2-Amino methyl pyridine compound of Formula IV to afford 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide compound of Formula III; and


iii) reacting 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamicle compound of Formula III with a reducing agent to afford flecainide.
Step i) involves reacting the compound 2,5-Bis(2,2,2-trifluoro ethoxy) benzoic acid of Formula V with a suitable chlorinating agent in the presence of a suitable organic solvent.
The chlorinating agents that may be utilized include thionyl chloride, phosphorous pentachloride, phosphorous trichloride, phosphorous oxychloride, oxalyl chloride and the like or mixtures thereof.
The solvents that may be utilized Include but are not limited to halogenated solvents such as dichloromethane, 1,2-dichloroethane, chloroform and carbon tetrachloride; hydrocarbon solvents such as toluene, xylene, n-heptane, cyclohexane and n-hexane; nitrile solvents such as acetonitrile and propionitrile; N, N-dimethylformamide (DMF) and N, N-dimethylacetamide or mixtures thereof.
The reaction is typically carried out at room temperature, however, if required the reaction may be carried out at higher temperatures as per the progress of the reaction.
Suitable temperatures for conducting the reaction range from about 10 °C to about 55 °C or from about 25 °C to about 35 °C.
The reaction can be conducted as long as required for the completion of the reaction, such as from about 30 minutes to about 5 hours, or longer. The reaction may be preferably carried out in the presence of an acid acceptor such as triethylamine.
Step ii) involves reacting the corresponding acid chloride intermediate with the compound 2-Amino methyl pyridine of Formula IV to afford the compound 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide of Formula III.

The reaction of the above obtained acid chloride with a compound of Formula IV may be carried out with or without isolation of the acid chloride intermediate. The reaction may be carried out in a non-reactive solvent. The reaction may be carried out at room temperature, however, if required the reaction may be carried out at higher temperatures whenever required.
The solvents that may be utilized for this step include halogenated solvents such as dichloromethane, 1,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertiarybutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as toluene, xylene, n-heptane, cyclohexane and n-hexane; nitrile solvents such as acetonitrile and propionitrile; dimethylsulfoxide (DMSO), DMF and N, N-dimethylacetamide; or mixtures thereof
Optionally, the reaction may be carried out in the presence of an acid scavenger. The acid scavenger that may be useful includes inorganic bases or organic bases. The bases that may be utilized for this step include but are not limited to inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium methoxide; organic bases such as triethyl amine, monomethyl amine, N,N-diethylethanamine, N-(1-methylethyl)-2-propanamine.
Step iii) involves the reduction of the compound 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide of Formula III with palladium on a support carrier in the presence of a solvent to afford flecainide of Formula II.
Suitable support carriers that can be utilized include carbon, alumina, calcium carbonate, barium carbonate, barium sulfate, strontium carbonate, sulfide carbon and silica gel. The amount of palladium is 5% or 10% w/w on support carrier.

All of the previous processes involve the use of plantinum-carbon catalyst for this reduction step, which increases the cost of manufacturing hence it may not be suitable at commercial level.
Surprisingly we have found that the use of palladium-carbon catalyst for this reduction step also provides excellent yield and purity.
The solvents that may be utilized for this step includes alcoholic solvents such as methanol, ethanol, isopropyl alcohol and n-propanol; halogenated solvents such as dichloromethane, 1,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertiarybutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as toluene, xylene, n-heptane, cyclohexane and n-hexane; nitrile solvents such as acetonitrile and propionitrile; DMSO, DMF and N, N-dimethylacetamide; water or mixtures thereof.
Suitably the reduction Is carried out in the presence of an acid such as acetic acid which would enhance the rate of reaction.
Suitable temperatures for conducting the reaction range from about 30 °C to about 150 °C, or from about 75 °C to about 140 °C, or the reflux temperature of the solvent used.
The reaction can be conducted as long as required for the completion of the reaction, such as from about 30 minutes to about 7 hours, or longer.
The molar equivalents of acetic acid can range from about 1 to about 5, per molar equivalent of the compound having Formula III.
The hydrogen pressure used can range from about 1 to about 10 kg/cm^.
Flecainide free base of Formula II obtained by the above process is characterized by its XRPD pattern having principal peaks at about 6.3, 12.8, 13.2, 15.9, 18.8, 20.3, 22.5, and 23.0, ± 0.2 degrees 2 theta and substantially as depicted in Fig. 2.
Flecainide prepared as above can be converted to an acid addition salt by reacting with an acid. In one embodiment the acid used is acetic acid to afford flecainide acetate of Formula I.

In another aspect the present application provides a process for the preparation of flecainide acetate by reacting flecainide of Formula II with acetic acid in a suitable solvent to afford flecainide acetate of Formula I.
Other suitable solvents that may be utilized for this step include but are not limited to alcoholic solvents such as methanol, ethanol, isopropyl alcohol and n-propanol; halogenated solvents such as dichloromethane, 1,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertlarybutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as xylene, n-heptane, cyclohexane and n-hexane; nitrile solvents such as acetonitrile and propionitrile; DMSO, DMF and N, N-dimethylacetamide; or mixtures thereof.
Suitable temperatures for conducting the reaction range from about 10°C to about 70°C, or from about 30°C to about 50°C.
The reaction can be conducted as long as required for the completion of the reaction, such as from about 30 minutes to about 5 hours, or longer.
Flecainide acetate obtained can be purified further by recrystallization or slurrying in suitable solvents.
The solvents that may be utilized for the purification of Flecainide or its acid addition salts either by recrystallization or by slurrying include but are not limited to methanol, ethanol, isopropyl alcohol and n-propanol; halogenated solvents such as dichloromethane, 1,2-dichloroethane, chloroform and carbon tetrachloride; ketone solvents such as acetone, ethylmethyl ketone and methyl isobutyl ketone; esters such as ethyl acetate, n-propyl acetate, n-butyl acetate, isobutyl acetate and t-butyl acetate; ether solvents such as diethyl ether, dimethylether, di-isopropylether, methyltertlarybutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as toluene, xylene, n-heptane, cyclohexane and n-hexane; nitrile solvents such as acetonitrile and propionitrile; DMSO, DMF and N, N-dimethylacetamide; v\/ater or mixtures thereof.
The solid thus obtained is recovered from the reaction mixture using suitable techniques such as decantation, filtration by gravity or by suction, centrifugation, and

the like in any form. Other techniques for separating the solids from the reaction mixtures are also within the scope of this invention.
The solid material obtained by any of the techniques described above may be further dried. Drying may be suitably carried out by any known methods such as tray dryer, vacuum oven, air oven, fluidized bed dryer, spin flash dryer, flash dryer. The drying can be carried out at temperatures of about 35° C to about 55° C under vacuum for a sufficient time ranging from 1 to 15 hours.
Typically, drying should be carried out at temperatures ranging from about 40 X to about 55 °C under a reduced pressure of about 630 to about 680 mm Hg to provide an acceptable physical appearance when made into solution using water.
The possible impurities in the above described process are (8aRS)-3-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyridine, (RS)-(Piperidin-2-yl)methanamine, 2,5- Bis(2,2,2-trifluoro ethoxy)benzoic acid, 2,5-Bis (2,2,2-trifluoro ethoxy)-N-(2-pyridyl methyl) benzamide, 2,5-Bis (2,2,2-trifluoro ethoxy)-N-[(1-methyl-2-piperidyl) methyl] benzamide and (RS)-4-hydroxy-N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy) benzamide.
Typically, Flecainide acetate of Formula I obtained by the process of the present invention is of high purity, such as at least about 99.0 wt %, or at least about 99.5 wt % or at least about 99.8%.
In another aspect, the present invention provides Flecainide acetate having total impurities less than about 1%, prefebably each impurity less than about 0.5%, more preferably less than about 0.2% and most preferably less than about 0.1%. Flecainide and its salts can be analyzed by techniques such as high performance liquid chromatography ("HPLC").
Flecainide acetate of Formula I obtained by the process of the present invention contains the residual solvents within the ICH limits. Flecainide acetate of Formula I obtained by the process of the present invention contains less than about 5000 ppm, or less than about 1000 ppm or less than about 500 ppm of isopropyl alcohol, less than about 890 ppm or less than about 500 ppm of toluene, less than about 3880 ppm or less than about 1000 ppm or less than about 500 ppm of cyclohexane, less than about 3000 ppm or less than about 1000 ppm, or less than about 500 ppm of methanol, less

than about 600 ppm or less than about 400 ppm or less than about 200 ppm of dichloromethane as determined by gas chromatography ("GC").
Flecainide acetate of Formula I obtained by the process of the present invention contains the acetic acid about 11 to 14%, preferably about 12 to 13.2% when analyzed by potentiometry.
Typically, flecainide acetate of Formula I obtained by the process of the present invention has a Dgo less than about 200 microns, preferably less than about 100 microns, D50 less than about 150 microns, preferably less than about 75 microns and D10 less than about 100 microns, preferably less than about 50 microns after micronisation using an air jet mill at a pressure greater than about 0.5-5 kg/cm^ air pressure.
Flecainide acetate of Formula I obtained by the process of the present invention is characterized by its XRPD pattern having principal peaks at about 6.0, 13.6, 15.3, 18.4, 20.6, 22.2, and 23.4, ± 0.2 degrees 2 theta which Is substantially as depicted in Fig. 3.
The XRPD of the crystalline forms of flecainide free base of Formula II and flecainide acetate of Formula I were measured on a Bruker AXS, DS Advance Powder X-ray powder Diffractometer with a Cu K alpha-1 radiation source.
In yet another embodiment, the present invention provides a pharmaceutical formulation comprising flecainide acetate of Formula I produced by a process of the present invention together with at least one pharmaceutically acceptable excipient.
The pharmaceutical composition comprising flecainide or its pharmaceutically acceptable salts of the invention along with one or more pharmaceutically acceptable carriers may further formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid oral dosage forms such as but not limited to syrups, suspensions, dispersions, and emulsions; and injectable preparations such as but not limited to solutions, dispersions, and freeze dried compositions. Formulations may be in the form of immediate release, delayed release or modified release. Further, immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of

hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir systems or combinations of matrix and reservoir systems. The compositions may be prepared by direct blending, dry granulation or wet granulation or by extrusion and spheronization. Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated or modified release coated. Compositions of the present invention may further comprise one or more pharmaceutically acceptable excipients.
Pharmaceutically acceptable excipients that find use in the present invention include, but are not limited to: diluents such as starch, pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar and the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pregelatinized starch and the like; disintegrants such as starch, sodium starch glycolate, pregelatinized starch, crospovidone, croscarmellose sodium, colloidal silicon dioxide and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants; complex forming agents such as various grades of cyclodextrins, resins; release rate controlling agents such as hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, ethylcellulose, methylcellulose, various grades of methyl methacrylates, waxes and the like. Other pharmaceutically acceptable excipients that are of use include but are not limited to film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants and the like.
The process of present invention is simple, cost effective, reproducible and robust to produce the compound flecainide and its salts, such as flecainide acetate of Formula I, with high yield and purity.
Certain specific aspects and embodiments of the present invention will be explained in greater detail with reference to the following examples, which are provided by way of illustration only and should not be construed as limiting the scope of the invention in any manner.

EXAMPLES EXAMPLE 1: PREPARATION OF 2,5-BIS(2,2,2-TRIFLUOROETHOXY) -N-(2-PYRIDYLMETHYL)BENZAMIDE (FORMULA III)
400 ml of dichloromethane, 40 g of 2,5-Bis(2,2,2-trifluoro ethoxy) benzoic acid of Formula V and 7 ml of triethylamine were charged into a clean and dry 4 neck round bottom flask under a nitrogen atmosphere, followed by stirring for 25 minutes. 11 ml of thionyl chloride was added slowly over 25 minutes under a nitrogen atmosphere followed by stirring for 2 hours. After completion of the reaction, 85% v/v of the solvent was distilled at 35 °C under vacuum. 80 ml of dichloromethane was charged followed by distillation of 80% v/v of the solvent on the total volume at 35 °C under vacuum. 800 ml of dichloromethane added to the crude and 16.3 g of 2-Amino methyl pyridine of Formula IV was added at 25-28°C for 25 minutes under a nitrogen atmosphere followed by stirring at 28°C for 1 hr 40 minutes. After completion of the reaction, the reaction was quenched by charging 320 ml of water. pH of the resultant reaction suspension was adjusted to 9.2 by the addition of 120 ml of 10% sodium carbonate solution. Organic and aqueous layers were separated and the organic layer was washed with 3x320 ml of demineralised water. Organic and aqueous layers were separated and about 85% v/v of the organic layer was distilled at 35 °C under vacuum. 80 ml of cyclohexane was charged followed by distillation of the solvent under vacuum to about 85% v/v of the initial volume. 400 ml of cyclohexane was charged followed by cooling to 28°C.The resultant suspension was stirred for 45 minutes followed by filtration of the separated solid and the solid was washed with 80 ml of cyclohexane. The solid obtained was dried at 55°C for 9 hours to afford 46 g of the title compound. Purity by HPLC: 99.3%.
EXAMPLE 2: PREPARATION OF 2,5-BIS(2,2,2-TRIFLUORO ETHOXY)-N-(2-PIPERIDYLMETHYL) BENZAMIDE (FORMULA II)
300 ml of methanol, 30 g of 2,5-bis (2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl) benzamide acetic acid of Formula III and 7.5 g of acetic acid were charged into a clean and dry autoclave vessel under a nitrogen atmosphere. 4.5 g of palladium on carbon (5 % wet type 39) in 15 ml of demineralised water was charged. The resultant suspension

was heated to 85°C and 5 kg /cm^ anhydrous hydrogen gas pressure was applied to the suspension for 5 hours. After completion of the reaction, the suspension was cooled to 28°C, the suspension was filtered through hyflow bed and was washed with 60 ml of methanol. The resultant filtrate was distilled completely at about 56°C under vacuum. 600 ml of water was charged to the residue followed by stirring for 35 minutes. The resultant solution was filtered through hyflow bed and washed with 60 ml of water. The filtrate was heated to about 54 °C followed by charging of 120 ml of toluene. The resultant mixture was stirred for 10 minutes, the organic and aqueous layers were separated. The aqueous layer was washed with 2x120 ml of toluene followed by charging of the aqueous layer into a clean and dry 4 neck round bottom flask. pH of the aqeous layer was adjusted to about 9.8 by the addition of 180 ml of 10% sodium carbonate solution over 20 minutes, followed by stirring for 35 minutes. Separated solid was filtered and the solid was washed with 150 ml of demineralised water. The solid obtained was dried at about 68 "C under vacuum over about 14 hours to afford 25 g of the title compound. Purity by HPLC: 99.67%.
EXAMPLE 3: PREPARATION OF FLECAINIDE ACETATE (FORMULA I)
20 g of 2,5-bis(2,2,2-trifluoro ethoxy)-N-(2-piperidylmethyl)benzamide of Formula II and 120 ml of toluene were charged into a clean and dry 4 neck round bottom flask followed by heating to 45°C. The resultant mixture was stirred for 30 minutes. 2 g of carbon was charged followed by stirring for 10 minutes. The suspension was filtered through hyflow and washed with 40 ml of toluene. The resultant filtrate was charged into a clean and dry round bottom flask.
4.35 g of acetic acid was dissolved in 20 ml of toluene, was filtered through hyflow and washed with 20 ml of toluene. The resultant acetic acid and toluene filtrate was added to the above flecainide filtrate over 30 minutes at 28°C followed by stirring for 1 hour 10 min. The separated solid was filtered and washed with 40 ml of toluene. Wet solid obtained was charged into a clean and dry round bottom flask followed by charging of 100 ml of toluene. The resultant suspension was stirred for about 90 minutes. The solid was filtered and washed with 40 ml of toluene followed by washing

with 20 ml of isopropyi alcohol. The solid obtained was dried at about 55 °C under vacuum for 12 hours to afford 18.4 g of the title compound. Purity by HPLC: 99.82%. Heavy metals: less than 20 ppm. Ash: 0.02% w/w.

We Claim:
1. A process for preparing flecainide or its salt comprising reduction of 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide compound of Formula III in a solvent in the presence of palladium on support carrier to afford 2,5-Bis(2,2,2-trifluoro ethoxy)-N-(2-piperidylmethyl)benzamide compound of Formula II.
2. The process of claim 1, wherein the solvent is selected from the group comprising of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, ethylacetate, isopropyl acetate, tertiary butyl acetate, toluene, xylene, cyclohexane, water and mixtures thereof.
3. The process of claim 1, wherein the reduction is performed in the presence of acetic acid.
4. The process of claim 1, wherein the palladium is 5% or 10% w/w on support carrier.
5. The process of claim 4, wherein the support carriers are selected from the group comprising of carbon, alumina, calcium carbonate, barium carbonate, barium sulfate, strontium carbonate, sulfide carbon and silica gel.
6. The process of claim 1, wherein the reduction is carried out at the temperature of about 40 to about 100 °C.
7. The process of claim 1, further comprises conversion of 2,5-Bis(2,2,2-trifluoro ethoxy)-N-(2-piperidylmethyl)benzamide compound of Formula II to its acid addition salt.
8. A process for the preparation of flecainide or its salt comprising the steps of
a) reacting 2,5-Bis(2,2,2-trifluoro ethoxy) benzoic acid of Formula V with a chlorinating agent in a organic solvent;

b) reacting the corresponding acid chloride intermediate obtained in step a) with
2-Amino methyl pyridine of Formula IV afford the compound 2,5-Bis(2,2,2-
trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide of Formula III;
c) reducing 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide of
Formula III in a solvent in the presence of palladium on support carrier to afford to
obtain flecainide; and
d) converting flecainide into its acid addition salts.
9. The process of claim 8, wherein step d) is carried out in toluene and the acid
addition salt is acetate.
10. A process for preparing flecainide acetate comprising the steps of:
a) reducing 2,5-Bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)-benzamide of Formula III in methanol and water in the presence of palladium on carbon to obtain flecainide; and
d) reacting flecainide with acetic acid in toluene.