FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (hereafter referred to as the compound-II) and/or salts thereof, which is useful as a key intermediate for the synthesis of Dronedarone (I) which is chemically known as N-{2-butyl-3-[4-(3-dibutylaminopropoxy) benzoyl]benzofuran-5-yl} methanesulfonamide. The process of the present invention further involves transformation of the said amine (the compound-II) into Dronedarone (referred to as the compound-I) and/or pharmaceutically acceptable salts thereof.
BACKGROUND OF THE INVENTION
The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should not be construed as an express or implied admission that such art is widely known or forms part of common general knowledge in the field.
Dronedarone (the Compound-I) is an anti-arrhythmic agent used for the prevention and treatment of atrial fibrillation. The drug is marketed as its hydrochloride salt (the compound-LHCl) by SANOFI AVENTIS under the trade name MULTAQ® in the form of oral tablets. It is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF). Dronedarone hydrochloride has the chemical name N-{2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]benzofuran-5-yl} methanesulfonamide, hydrochloride and is generally represented as follows;

Dronedarone being an important anti-arrhythmic agent; a number of processes for its preparation as well as for its intermediates are known in the art.
US Patent No. 5,223,510 describe a process for the synthesis of Dronedarone through the amine intermediate compound-II, which is illustrated below in Scheme-I. In the process, (2-butyl-5-nitrobenzofuran-3-yl)(4-hydroxyphenyl)methanone (IV) is reacted with N-butyl-N-(3-chloropropyl)butan-l-amine (V) in the presence of potassium carbonate in methyl ethyl ketone to obtain (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl) methanone (III). The obtained compound-Ill is reduced to corresponding amine as (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino) propoxy)phenyl)methanone (II) in the presence of platinum oxide under hydrogen pressure. The specification of US'510 also suggests the use of palladium oxide, zinc in a hydrochloric acid medium or tin in a hydrochloric acid medium for the reduction of nitro compound. The amine (II) is subsequently converted to Dronedarone.
Scheme-I
US patent application 2013/0165675 describes a process for the synthesis of 5-amino-benzoyl-benzofuran derivative comprising reducing a 5-nitrobenzofuran derivative (III) by means of a hydrogen-transfer agent, in the presence of palladium-on-charcoal as catalyst and in an ether or a mixture of ethers as solvent.
Indian Published Patent Application 1080/CHE/2010 ("the IN'1080 Application") describes a process for the synthesis of Dronedarone and the intermediates thereof, comprising reduction of

(2-butyl-5-nitrobenzofliran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (III) in presence of a metal catalyst and ammonium formate, to obtain its corresponding amine.
Published PCT application WO-A-2012/153225 describes a process for the preparation of Dronedarone HC1 comprising a step of reducing 2-n-butyl-3-(4-(3-dibutylaminopropoxy) benzoyl)-5-nitrobenzofuran (III) in presence of Pd/C in mixture of ethyl acetate and acetic acid under hydrogen pressure to obtain 2-n-butyl-3-(4-(3-dibutylaminopropoxy)benzoyl)-5-amino benzofuran (II).
Indian patent application 3089/MUM/2010 describes a process for the preparation of 2-n-butyl-3-[4-(3-di-n-butylamino-propxy) benzoyl]-5-nitro benzofuran (III) from the reactants 2-n-butyl-3-(4-hydroxy benzoyl)-5-nitrobenzofuran (IV) and l-chloro-3-di-n-butylamino propane (V); in the presence of a base and a solvent other than methyl ethyl ketone in the presence of phase transfer catalyst.
Published PCT application WO-A-2012120544 describes a process for the preparation of 2-n-butyl-3-[4-(3-di-n-butylamino-propxy) benzoyl]-5-nitro benzofuran (III) by the reaction of l-chloro-3-(di-n-butylamino)propane (V) with 2-n-butyl-3->(4-hydroxy benzoyl)-5-nitrobenzofuran (IV) in a biphasic system comprising an aqueous phase containing an inorganic base, an organic phase and a phase transfer catalyst.
Several methods for the preparation of Dronedarone and its intermediates are known in the art such as published PCT applications WO-A-2012004658, WO-A-2012007959, WO-A-2012032545A1, WO-A-2012052448 and WO-A-2012120544; published Indian patent applications such as 3264/MUM/2010, 0654/MUM/2011 and 0629/CHE/2011.
It is evident from the discussion of the processes for the preparation of the (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (the compound-II), described in the afore cited patent documents that some of the reported processes primarily involve critical reaction conditions, costly reagents and catalysts such as platinum oxide and

phase transfer catalyst, use of complex reagents, purification using column chromatography and expensive solvents; which renders the process costlier and hence the processes are not industrially feasible.
In view of these drawbacks, there is a need to develop an industrially viable commercial process for the preparation of Dronedarone and its intermediates; which is simple, efficient and cost-effective process and provides the desired compounds in improved yield and purity.
Inventors of the present invention have developed an improved process that addresses the problems associated with the processes reported in the prior art. The process of the present invention does not involve use of any toxic and/or costly catalyst, solvents and reagents. Moreover, the process does not require additional purification steps and critical workup procedure. Accordingly, the present invention provides a process for the preparation of Dronedarone and its intermediates, which is simple, efficient, cost effective, environmentally friendly and commercially scalable for large scale operations.
SUMMARY OF THE INVENTION
In one aspect, the present invention relates to an improved process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamirio)propoxy)phenyl)methanone (compound II), comprising reducing the compound-Ill (as described herein) in the presence of a metal catalyst and ammonium chloride.
In one aspect, the present invention relates to an improved process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (compound II), comprising reducing the compound-Ill (as described herein) in the presence of zinc and ammonium chloride.
In another aspect, the present invention relates to improved process for the preparation of (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (the compound-III), comprising reacting the compound-lV (as described herein) with the compound-V (as

described herein) in presence of a base and a solvent mixture essentially Consisting of water; wherein the reaction is in the absence of a phase transfer catalyst.
In another aspect, the present invention relates to a one pot process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (compound-II), comprising (a) reacting the compound-IV (as described herein) with the compound-V (as described herein) in presence Of a base and a solvent mixture to obtain the compound-Hi (as described herein), (h) in-situ reduction of the compound-Ill in the presence of a metal catalyst and ammonium chloride.
In another aspect, the present invention relates to one pot process for the preparation of 5-amino-
2-butylbenzofufan-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (compound-II),
comprising (a) reacting the compound-IV (as described herein) with the compound-V (as described herein) in presence of a base and solvent mixture essentially consisting of water to obtain the compound-Ill (as described herein); (b) in-situ reduction of the compound-Ill in the presence of zinc and ammonium chloride; wherein, the step-(a) is in absence of a phase transfer catalyst.
According to another aspect of the present invention, there is provided an improved process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino) propoxy)phenyl) methanone (compound-II), wherein the product oxalate salt of compound-II has purity of about 98%.
According to another aspect of the present invention, there is provided an improved process fdr the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino) propoxy)phenyl) methanone (compound-II), wherein the product compound II free base has purity of about 98%.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention relates to an improved process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyI)methanone (the compound

II) represented by the following formula,
comprising reducing the compound-Ill represented by the following formula;
in the presence of a metal catalyst and ammonium chloride.
The compound-II obtained by the afore described process is optionally, converted into Dronedarone free base or a pharmaceutically acceptable salt thereof.
Accordingly, there is provided an improved process for the preparation of Dronedarone or a pharmaceutically acceptable salt thereof; comprising the steps of:
(a) preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound II) represented by the following formula,

by reducing the compound-Ill represented by the following formula;
Compound-Ill in the presence of a metal catalyst and ammonium chloride; and
(b) optionally, converting the compound-II into dronedarone free base or a pharmaceutical^ acceptable salt thereof.
In the context of the present invention, the term "optionally" when used in reference to any element; including a process step e.g. conversion of a compound; it is intended to mean that the subject element is subsequently converted, or alternatively, is not converted to a further compound. Both alternatives are intended to be within the scope of the present invention.
In an embodiment, the metal catalyst is selected from the group consisting of zinc (Zn), iron (Fe) or tin (Sn).
In an embodiment, the metal catalyst is zinc.
Accordingly, in an embodiment the present invention relates to a process for the preparation of of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound II) represented by the following formula,

Compound-II comprising reducing the compound-Ill represented by the following formula;
in the presence of zinc and ammonium chloride.
In a specific embodiment, the process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound-II) comprises the steps of:
(1) dissolving compound (III) in a solvent;
(2) adding a metal catalyst to the reaction mixture of step (1);
(3) cooling the reaction mixture of step (2) to a temperature of about 20 °C;
(4) adding ammonium chloride solution to the reaction mixture of step (3);
(5) stirring the reaction mixture of above step (4) at temperature of about 35 °C; and
(6) isolating the desired product.
The process of the present invention as per the specific embodiment described above is illustrated in the following Scheme-II,

Seheme-II
The process as described above further comprises optionally, converting the pure compound-II into Dronedarone as a free base or a pharmaceutically acceptable salt thereof,
The solvent used in the step-(l) of the above process (as depicted in the Scheme II) is selected from an alcoholic solvent such as methanol, ethanol, isopropanol, t-amyl alcohol, t-butyl alcohol and hexanol; halogenated solvent such as dichloromethane, 4-bromotoluene, diiodomethane, carbon tetrachloride, chlorobenzene and chloroform; ketone such as acetone; an ether solvent such as tetrahydrofuran, cyclopentyl methyl ether, 2-methyltetrahydrofuran, diethyl ether and 1,4-dioxane; an aprotic solvent such as acetonitrile, N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide, dimethyl sulfoxide (DMSO) and N-methylpyrrolidone (NMP); an aromatic solvent such as toluene, xylene and benzene; water or a mixture thereof.
The metal catalyst used in the step-(2) of the above process (as depicted in the Scheme II) is selected from the zinc (Zn), iron (Fe) or tin (Sn). More preferably, the metal catalyst is zinc.
The term 'temperature of about 20 °C referred to in the step (3) of the above process (as
depicted in the Scheme II) can range from 15 °C to 25 °C.
The term 'temperature of about 35 °C referred to in the step (5) of the above process (as

depicted in the Scheme II) can range from 30 °C to 40 °C.
The term 'isolating the desired product' referred to in step (6) corresponds to the steps involving addition of water, biphasic solvent workup, separation of solvent layers, evaporation of solvent, filtration, washing and drying.
The process of the present invention as illustrated in the above Scheme-II comprises addition of methanol to the compound-Ill, followed by the addition of zinc dust. The resulting reaction mixture was cooled to a temperature of about 20 °C. Aqueous solution of ammonium chloride was slowly added to the said reaction mixture. The reaction mixture was further heated and stirred at a temperature of about 35 °C. The reaction mixture was extracted in ethyl acetate and treated with sodium chloride. The combined organic layer was evaporated to afford the amine compound as 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (II) which was subsequently converted to its oxalate salt of purity about 98% (HPLC).
In another aspect, the present invention relates to an improved process for the preparation of (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (the compound-Ill) represented by the following formula,
comprising reacting the compound-IV represented by the following formula,

Compound-IV with the compound-V represented by the following formula,
in presence of a base and a solvent mixture essentially consist of water; wherein the reaction is in absence of a phase transfer catalyst.
Accordingly in yet another aspect, the present invention relates to an improved one pot process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound-ID represented by the following formula,
comprising the steps of,
(A) reacting a compound-IV represented by the following formula;

with the compound-V represented by the following formula;
in presence of a base and a solvent mixture essentially consisting of water;
(B) 'in-situ' reducing the compound-Ill obtained from the step (A) represented by the following formula,
in the presence of a metal catalyst and ammonium chloride; wherein, the step-(A) is in the absence of a phase transfer catalyst.
The compound-II obtained by the afore described process is optionally, converted into Dronedarone as a free base or a pharmaceutically acceptable salt thereof.
Accordingly, there is provided an improved one pot process for the preparation of Dronedarone or a pharmaceutically acceptable salt thereof; comprising the steps of: (X) preparation of (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl) methanone (the compound III) represented by the following formula,

by reacting a compound-IV represented by the following formula;
with the compound-V represented by the following formula;
in presence of a base and a solvent mixture essentially consisting of water; in absence of a phase
transfer catalyst;
(Y) preparation of compound (II) represented by the following formula,

by 'in-situ' reduction of compound-Ill obtained from the step (A) in the presence of a metal catalyst and ammonium chloride; and
(Z) optionally, converting the compound-II into dronedarone as a free base or a pharmaceutically acceptable salt thereof.
In the context of the present invention, the term "optionally" when used in reference to any element; including a process step e.g. conversion of a compound; it is intended to mean that the subject element is subsequently converted, or alternatively, is not converted to a further compound. Both alternatives are intended to be within the scope of the present inventibn.
In an embodiment, the base is an inorganic base.
In an embodiment, the inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, cesium carbonate, calcium carbonate, sodium hydroxide and potassium hydroxide.
In an embodiment, the inorganic base is potassium carbonate.
In an embodiment, the solvent mixture is selected from the group consisting of an alcohol such as methanol, ethahol, n-propyl alcohol, isopropyl alcohol, isobutyl alcohol and hexanol; an ether solvent such as diethyl ether, diisopropyl ether, 1,4-dioxane, methyl tert-butyl ether > tetrahydrofuran, 1,3 dioxolane, cyclopentyl methyl ether, 2-methyltetrahydrofuran; an aprotic solvent such as acetonitrile, N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide, dimethyl sulfoxide (DMSO) and N-methylpyrrolidone (NMP); an aromatic solvent such as toluene, xylene and benzene; a ketone such as acetone; water and/or a rhixture thereof.
In an embodiment, the solvent mixture consists of an organic solvent and water.
In an embodiment, the mixture of solvents comprises organic solvent and water in a ratio ranging from 1:1 to 10:10 as v/v (volume/volume). Preferably, the ratio of the organic solvent to the water ranges from 1:1 to 10:5 as v/v (volume/volume).
In an embodiment, the organic solvent in the solvent mixture is selected from an aromatic hydrocarbon, a halogenated hydrocarbon, an alcohol, an ester, an ether, a ketone, a nitrile, an

amide, a sulfoxide, a lactam, or a mixture thereof.
In the context of the present invention, the term "ratio" when used with respect to any element e.g. solvent; it is intended to mean that the subject element consists of v/v (volume/volume) ratio ranging from 1:1 to 10:10 of the organic solvent to water. All the possible permutation and combination alternatives of v/v ratio are intended to be within the scope of the present invention.
In an embodiment, the solvent mixture is selected from dioxolane and water.
In an embodiment, the solvent mixture is selected from 1,3-dioxolane and water.
In an embodiment, the mixture of solvents comprises dioxolane and water in the v/v ratio of 3v: lv (dioxolane: water).
In an embodiment, the solvent mixture comprises 1,3-dioxolane and water in the v/v ratio of 3v: lv (1,3-dioxolane: Water).
In an embodiment, the metal catalyst is selected from the group consisting of zinc (Zn), iron (Fe) or tin (Sn).
In an embodiment, the metal catalyst is zinc.
In a specific embodiment, the process for the preparation of 5-amino-2-butylbenzofuranr3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound-II) comprises the steps of:
(i) dissolving compound (IV) in a solvent mixture;
(ii) adding a base to the reaction mixture of step (i);
(iii) adding compound (V) to the stirring reaction mixture of step (ii);
(iv) heating the reaction mixture of step (iii) to a temperature of about 80 °C;
(v) adding a metal catalyst to the reaction mixture of step (iv) at room temperature;
(vi) cooling the reaction mixture of step (v) to a temperature of about 20 °C;

(vii) adding ammonium chloride solution to the reaction mixture of step (vi);
(viii) stirring the reaction mixture of above step (vii) at temperature of about 35 °C; and
(ix) isolating the desired product.
The process of the present invention as per the specific embodiment described above is illustrated in the following Scheme-Ill,
The process as described above further comprises optionally, converting the pure compound-II into dronedarone as a free base or a pharmaceutically acceptable salt thereof.
The solvent mixture used in the step-(i) of the above process (as depicted in the Scheme III) is selected from the group consisting of an alcohol such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, isobutyl alcohol and hexanol; an ether solvent such as diethyl ether, diisopropyl ether, 1,4-Dioxane, Methyl tert-butyl ether, tetrahydrofuran, 1,3 dioxolane,

cyclopentyl methyl ether* 2-methyltetrahydrofuran; an aprotic solvent such as acetonitrile, N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide, dimethyl sulfoxide (DMSO) and N-methylpyrrolidone (NMP); an aromatic solvent such as toluene, xylene and benzene; a ketone such as acetone; water and/or a mixture thereof. More preferably, the solvent mixture is 1,3 dioxolane: water.
The base used in the step-(ii) of the above process (as depicted in the Scheme III) is an inorganic base selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, cesium carbonate, calcium carbonate, sodium hydroxide and potassium hydroxide. More preferably, the base is potassium carbonate.
The term 'temperature of about 80 °C referred to in the step (iv) of the above process (as depicted in the Scheme III) can range from 70 °C to 80 °C.
The metal catalyst used in the step-(v) of the above process (as depicted in the Scheme III) is selected from the zinc (Zn), iron (Fe) or tin (Sn). More preferably, the metal catalyst is zinc.
The term 'temperature of about 20 °C referred to in the step (vi) of the above process (as depicted in the Scheme II) can range from 15 °C to 25 °C.
The term 'temperature of about 35 °C referred to in the step (viii) of the above process (as depicted in the Scheme II) can range from 30 °C to 40 °C.
The term 'isolating the desired product' referred to in the step (ix) corresponds to the steps involving addition of water, biphasic solvent workup, separation of solvent layers, evaporation of solvent, filtration, washing and drying.
The process of the present invention as illustrated in the above Scheme-Ill comprises reaction of the compound (IV) with compound (V) in the presence of an inorganic base selected from potassium carbonate, in a mixture of 1,3 dioxolane and water as the solvent, wherein the v/v ratio of 1,3 dioxolane with respect to water is 3 v: 1 v (1,3 dioxolanerwater). The reaction mixture was heated to a temperature of 75-80 °C for about 3 hours to obtain product as compound (III). The

nitro compound-Ill was reduced using zinc and aqueous ammonium chloride. The reaction mixture was extracted using ethyl acetate and washed with brine solution. The combined organic layer was treated with oxalic acid solution and stirred at a temperature of about 30 °C for 10-12 hours. The reaction mixture was cooled to 0-5 °C and solid oxalic acid salt of (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (compound-II) obtained as a precipitated product was isolated by filtration in a yield of about 85 % and purity of about > 98 % (HPLC).
Accordingly, in an embodiment the present invention relates to a process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound II) represented by the following formula,
comprising the steps of,
(F) reacting a compound-IV represented by the following formula;
with the compound-V represented by the following formula;

Compound-V
in presence of a base and 1,3 dioxolane:water as solvent mixture; in absence of a phase transfer catalyst.
(G) 'in-situ' reducing the compound-Ill obtained from the step (A) represented by the following formula,
in the presence of zinc and ammonium chloride.
Inventors of the present invention also observed the effect of solvent ratio over the purity of compound-Ill; as summarized in below Table-1:

Ratio of l,3-Dioxolane:water Volume of solvent Purity HPLC (%)
3:1 3V 98.4
2:1 3V 97.7
3:1 3V 97.9
1:1 3V 98.3
1:2 3V 95.5
Table-1
The pure product, of (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl) methanone (the compound-II) was further converted to Dronedarone as a free base or a pharmaceutically acceptable salt thereof by a process known in the art, for instance, the process described in US patent No. 5,223,510; wherein the (5^amino-2-butylbenzofuran-3-yl)(4-(3-

(dibutylamino)propoxy)phenyl)methanone (the compound-II) is converted to corresponding mesyl intermediate compound and subsequently transformed into Dronedarone.
Advantageously, the process of present invention is simpler and it overcomes the drawbacks of the known methods.
Advantageously, the process of present invention provides product with significant improvements in the purity and yield over the processes reported in the prior art. Hence the process of the instant invention effectively contribute to the reduction of overall cost of the process.
The invention is further illustrated by the following examples which are provided to be exemplary of the invention, and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
EXAMPLES
Example-1: Preparation of oxalic acid salt of (5-amino-2-butylbenzofuran-3-yl)(4-(3-
(diburylamino)propoxy)phenyl)methanone (compound-II)
1,3-dioxolane (200.0 mL) and water (100.0 mL) were charged in a flask followed by the addition of (2-Butyl-5-nitrobenzofuran-3-yl)(4-hydroxyphenyl)methanone (100.0 g), potassium carbonate (40.69 g) and N-butyl-N-(3-chloropropyl)butan-l-amine (72.69 g). The reaction mixture was heated at a temperature of about 75-80 °C for 3 hours. The reaction mixture was cooled to a temperature of about 25-35 °C and was added 400 mL of ethyl acetate and 200 mL of water to it. The separated ethyl acetate layer was washed with 200 mL of 20 % brine solution. The combined organic layer was concentrated under vacuum at 35-50 °C. To the obtained mixture, was added 350 mL of methanol followed by zinc dust (154 g) and aqueous ammonium chloride solution (400 mL) [127.5 g in 350 mL water]. The reaction mixture was stirred at a temperature of about 25-35 °C for 3-5 hors. 400 mL of ethyl acetate was added to the reaction

mass and filtered. The filtrate was treated with solid NaCl (25 g) and the separated organic layer was washed with 300 mL 20 % brine solution. To the separated organic layer, was added -200 mL oxalic acid solution (100 g oxalic acid in 150 mL of methanol) and stirred at a temperature of about 30 °C for 10-12 hours. The reaction mixture was cooled to 0-5 °C temperature and the precipitated solid was filtered to obtain the title oxalic acid salt of amine compound (II) [%Yield: 85 %, Purity: 98 % (HPLC)]
Example-2: Preparation of (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (compound-II)
Methanol (300.0 mL) was charged into a flask followed by the addition of (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino) propoxy) phenyl) methanone (compound III) (100 g), 400 mL aqueous ammonium chloride solution (105.2 g ammonium chloride in 300mL of water) and zinc dust (126.8 g) . The reaction mixture was heated at a temperature 50°C for 3-5 hr. The organic layer was evaporated followed by the addition of ethyl acetate (400 mL) and water (200 mL) to reaction mass. The separated organic layer was treated with brine solution. The combined organic layer evaporated under vacuum to obtain the title amine compound (II) [%Yield: 97%, Purity: 98% (HPLC)].

We Claim
1. A process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (II) of following formula,
Compound-II comprising; reducing the compound-Ill of following formula;
Compound-Ill in the presence of a metal catalyst and ammonium chloride. 2. A process for the preparation of (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino) propoxy)phenyl)methanone (III) of following formula,
comprising; reacting the compound-IV of following formula

Compound-IV with the compound-V of following formula;
Compouhd-V in the presence of a base and a solvent mixture essentially consisting of water; wherein the reaction is in the absence of a phase transfer catalyst.
3. A one pot process for the preparation of 5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy) phenyl)methanone (the compound-II) of following formula,
Compound-II comprising the steps of, (A) reacting a compound-IV of following formula,

Compound-IV with the compound-V represented by the following formula;
Compound-V
in the presence of a base and a solvent mixture essentially consisting of water; to obtain compound-Ill of following formula,
Compound-Ill
(B)'in-situ' reducing the compound-Ill obtained from the step-(A) in the presence of a metal catalyst and ammonium chloride; wherein, the step-(A) is in the absence of a phase transfer catalyst.
4. The process according to claim I or claim 3, wherein the metal catalyst is selected from zinc (Zn), iron (Fe) or tin (Sn).
5. The process according to claim 2 or claim 3, wherein the base is selected from sodium carbonate, potassium car bon&te, sodium bicarbonate, cesium carbonate, calcium

carbonate, sodium hydroxide or potassium hydroxide.
6. The process according to claim 2 or step-A of claim 3, wherein the solvent mixture is a mixture of organic solvent and water in a ratio ranging from 1:1 to 10:10 as v/v (volume/volume).
7. The process according to claim 6, wherein the organic solvent is selected from an aromatic hydrocarbon, a halogenated hydrocarbon, an alcohol, an ester, an ether, a ketone, a nitrile, an amide, a sulfoxide, a lactam, or a mixture thereof.
8. The process according to claim 2 or step-A of claim 3, wherein the solvent mixture is a mixture of 1,3-dioxolane and water.
9. The process according to any one of the preceding claims, wherein the compound-II is further converted into Dronedarone as a free base or a pharmaceutically acceptable salt thereof.