Title of Invention	PROCESS FOR PREPARATION OF 3-ETHOXY-4-(ETHOXY CARBONYL)- PHENYL ACETIC ACID, AN INTERMEDIATE OF REPAGLINIDE
Abstract	Disclosed herein an efficient and cost effective process for preparation of 3-Ethoxy-4-(ethoxycarbonyl)-phenyl acetic acid , a key intermediate used in the preparation of an anti-diabetic drug, Repaglinide, which involves non-hazardous and cost effective raw materials making the process simple, economical and industrially viable.

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FORM 2 THE PATENT ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION: "Process for preparation of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid, an intermediate of Repaglinide" 2. APPLICANT (S) (a) NAME: Tytan Organics Pvt. Ltd. (b) NATIONALITY: Indian Company incorporated under the Indian Companies ACT, 1956 (c) ADDRESS: Sunama House, 3rd floor, August Kranti Marg, Mumbai - 400 026, Maharashtra, India 3. PREAMBLE TO THE DESCRIPTION The following specification particularly describes the invention and the manner in which it is to be performed. Field of invention: The present invention relates to an efficient and cost effective process for preparation of 3-Ethoxy-4-(ethoxycarbonyl)-phenyl acetic acid (V), a key intermediate in the preparation of an anti-diabetic drug, Repaglinide of formula (VI). More particularly, the present invention relates to an improved process for preparation of compound (V), which involves non-hazardous and cost effective raw materials making the process simple, economical and industrially viable. Background of the invention: Repaglinide, S (+) 2- ethoxy-4-{N-{l-(2-piperidinophenyl) -3-methyl-l-butyl}-aminocarbonylmethyl] benzoic acid (Formula VI) is known from US 5,216,167 and 5,312,924. Repaglinide is the first member of type II non-insulin dependent diabetes mellitus (NIDDM); a new class of oral hypoglycemic agents (meglitinides). It stimulates the secretion of insulin from beta cells in the pancreas, acting via calcium channels. Hypoglycemic events are less with Repaglinide as compared to other anti-diabetic agents. It offers a significantly better biological profile as compared to other sulphonyl urea class of hypoglycemic agents and approved by the U.S. FDA for treatment of non-insuline dependent diabetes mellitus (type-II diabetes). US application 2004192955 discloses a process for the preparation of ethyl 3-ethoxy-4-ethoxycarbonyl-phenylacetate of formula (V) which comprises of reacting 4-methyl salicylic acid with diethyl sulfate in presence of potassium carbonate in polar organic solvent at temperature 50-80° C for 6-12 hrs, the product obtained was filtered and the organic solvent was distilled to obtain the residue of ethyl-2-ethoxy-4-methylbenzoate which was further reacted with N-bromosuccinamide in carbon tetrachloride at temperature 40-60° C to obtain ethyl-4-bromomethyl-2-ethoxy benzoate. The obtained compound was reacted with carbon monoxide in ethyl alcohol at temperature of 30-50° C. for 14-24 hrs, in the presence of a palladium catalyst to obtain ethyl 3-ethoxy-4-ethoxycarbonyl-phenylacetate. US6686497 describes the process for the preparation of 3-ethoxy-4-(ethoxycarbonyl)-phenyl acetic acid which comprises of reacting 4-methylsalicylic acid with ethyl bromide in dimethylsulphoxide in presence of potassium carbonate at temperature within a range ambient to 100°C preferably 30-40° C during a period of one to several hours to obtain ethyl 2-ethoxy-4-methylbenzoate. The compound obtained was reacted with n-butyl lithium in a solution of di-isopropyl amine in tetrahydrofuran and hexamethyl phosphoramide and further reacted with carbon dioxide at -75 .degree.. C to give 3-ethoxy- 4-(ethoxy carbonyl)-phenyl acetic acid. ; One of the steps was performed at very low temperature -75.degree C, which impacted the efficiency of the process as a bottleneck. The recovery and reuse of the solvents tetrahydrofuran and dimethylsufoxide on scale up makes the process cumbersome. A need to develop a more efficient process was felt by the present inventors by overcoming the above said disadvantages. Journal of Medicinal Chemistry 1998 Vol.41, No.26, 5219 describes the process for the preparation of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid which comprises of reacting 2-Hydroxy-4-methyl-benzoic acid with ethyl bromide in the presence of K2CO3 in acetone at 150 °C for 30 hrs to give Ethyl-2-ethoxy-4-methyl-benzoate. The compound obtained was reacted with N-Bromo Succinamide to yield Ethyl-4-bromomethyl-benzoate which was further reacted with sodium cyanide in the presence of N-benzyl-tri-n-butylammonium chloride at 20 °C for 43 hrs to give Ethyl-4-cyanomethyl-2-ethoxy-benzoate. The cyano methyl ester obtained was treated with acid in ethanol which to give Ethyl-2-ethoxy-4-ethoxycarbomethyl-benzoate which was further hydrolyzed to give 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid. US publication 20040249188 discloses the process for the preparation of 3-Ethoxy-4-(alkoxy carbonyl)-phenyl acetic acid which comprises of reacting (2-Hydroxy-4-methyl) benzoic acid with diethyl sulfate using potassium carbonate in toluene to give Ethyl-2-ethoxy-4-methyl-benzoate which was reacted with N-Bromo Succinamide to give Ethyl-4-bromomethyl-2-ethoxy-benzoate. The compound obtained on cyanation yields the cyano compound which on hydrolysis gives the diacid compound. The diacid compound on esterfication in presence of trimethyl amine in toluene to yield Alkyl-2-ethoxy-4-alkoxy carbonyl methyl-benzoate which on further hydrolysis gives 3-Ethoxy-4-(alkoxy carbonyl)-phenyl acetic acid. The process as described above involve use of N-bromosuccinamide as brominating agent which is a costly raw material which gives rise to sudden exotherm in the reaction and leads to chance of runaway reaction during scale up. These processes also result in low yield with longer reaction time and also with associated problems in recovery of the solvents used in the reaction such as dichloromethane, being poor. , Another disadvantage is the use of weak bases like potassium carbonate, sodium carbonate, where carbondioxide was produced as by product. Formation of carbon dioxide leads to frothing during scale up which makes the process tedious to operate on industrial scale. Further, the prior art processes involve an additional extraction step with toluene to remove the inorganic impurities. The prior art processes have another disadvantage that cyclohexane was used with toluene as a solvent system for co-precipitation of the product. Separation of this co-solvent system is an additional step involved in the process with longer hour maintenance reaction of the manufacturing process for production of compound of formula (V). The methods for synthesis of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid of formula (V) as described above in references, Journal of Medicinal Chemistry 1998, Vol. 41, PP. 5219-5246 as well as U.S. patent application No.20040249188 by Reddy, Manne Satyanarayana et.al, December 2004, have limitations as above, which the present inventors have addressed through this invention. It is, therefore desirable to solve the problems associated with the prior art and to provide an efficient process for the preparation of 3-ethoxy-4- (ethoxy carbonyl)- phenyl acetic acid which improves the economics by employing less expensive and less hazardous raw materials which are easy to handle and is more productive. The process avoids the tedious and cumbersome procedures of recrystallization or purification techniques and is economical and convenient to operate on a commercial scale. Therefore, the process of present invention is cost effective, industrially viable and eco-friendly over prior art procedures. Objectives of the invention: The main object of the present invention is to provide a simple, commercially viable, efficient and cost effective process for the preparation of 3-Ethoxy-4- (ethoxy carbonyl)-phenyl acetic acid represented by formula (V), which obviates the drawbacks of the prior art processes. Summary of the Invention: According to the present invention, mere is provided the process for preparation of 3-ethoxy-4- (ethoxy carbonyl)-phenyl acetic acid of formula (V), an intermediate for synthesis of Repaglinide. The present invention discloses a process for the preparation of 3-Ethoxy-4-(ethoxy carbonyl) phenyl acetic acid of Formula (I) comprising the steps of: a) reacting 4-methyl salicylic acid of formula (VII) or potassium salt of formula (VII) with ethylating agent using base and suitable solvent to obtain compound of formula (I); b) halogenating the compound of formula (I) with suitable halogenating agent in the presence of hydrogen peroxide and a catalyst in suitable solvent to obtain ethyl-4-halomethyl-2-ethoxybenzoate of formula (II); c) cyanating the compound of formula (II) with sodium cyanide in the presence of phase transfer catalyst in suitable solvent system to obtain Ethyl-4-cyanomethyl-2-ethoxybenzoate of formula (III); d) treating the compound of formula (III) with and acid as catalyst in presence of solvent under anhydrous conditions, e) neutralizing the resultant reaction mass of step (d) using base to obtain diester of formula (IV), f) hydrolyzing compound of formula (IV) with 8-10% solution of the base at temperature ranges from 15-30°C preferably 20-25°C in a period of 2 hour; g) isolating 3-ethoxy-4-(ethoxycarbonyl)- phenyl acetic acid of formula (V) by extracting with suitable solvent and conventional acidification technique. Intermediates involved in Preparation of 3-Ethoxy-4-(ethoxy carbonyl)phenyl acetic acid are as follows: Detailed Description of the Invention: The present invention describes an improved and convenient process for the preparation of 3-Ethoxy-4- (ethoxy carbonyl)-phenyl acetic acid of formula (V). In one embodiment, the present invention describes a process for preparation of compound of formula (V) comprising the steps of; a) reacting 2-hydroxy-4-methyl benzoic acid of formula (VII) or potassium salt of formula (VII) with ethylating agent using base and suitable solvent to obtain compound of formula I; b) halogenating the compound I with halogenating agent in the presence of hydrogen peroxide and a catalyst in suitable solvent to obtain Ethyl-4-halomethyl-2-ethoxybenzoate of formula (II); c) cyanating the compound of formula (II) with sodium cyanide in the presence of a phase transfer catalyst in suitable solvent system to obtain Ethyl-4-cyanomethyl-2-ethoxybenzoate of formula (III); d) treating the compound of formula (III) with an acid as catalyst in presence of solvent under anhydrous conditions, e) neutralizing the resultant reaction mass of step (d) using base to obtain diester of formula (IV),and f) hydrolyzing compound of formula (IV) with 8-10% solution of the base at temperature ranges from 15-30°C preferably 20-25°C in a period of 2 hour; g) isolating 3-ethoxy-4-(ethoxycarbonyl)- phenyl acetic acid of formula (V) by extracting with suitable solvent and conventional acidification technique. The process of the present invention for preparation of 3-Ethoxy-4- (ethoxy carbonyl)-phenyl acetic acid of formula (V) which provides reaction of compound of formula (VII) with ethylating agent in presence of aqueous base, which is a strong base in suitable solvent at temperature ranges from 50°C - 150 °C preferably 100°C-110 °C for a time period 2 to 4 hour. The compound of formula (I) on halogenation with suitable halogenating agent in the presence of hydrogen peroxide and a catalyst in suitable solvent at temperature ranges from 30°C to 75 °C preferably 70-75 °C for a time period 2 - 4 hour resulted in Ethyl-4-halomethyl-2-ethoxybenzoate of formula (II). The compound of formula (II) on cyanation with sodium cyanide in the presence of a phase transfer catalyst in suitable solvent results in Ethyl-4-cyanomethyl-2-ethoxybenzoate of formula (III). The compound of formula (III) is converted to diester compound of formula (IV) by treating with an acid as catalyst in organic solvent at reflux temperature for a time period 15 to 20 hours under anhydrous conditions. The resultant reaction mass is neutralized using gaseous ammonia to remove acidity and to maintain anhydrous conditions of reaction mass. The compound of formula (IV) is then selectively hydrolysed with an acid to give 3-Ethoxy-4-ethoxycarbonyl-phenyl acetic acid of formula (V). Compound (IV) dissolved in neutral solution is converted to compound of formula (V) without recovery of solvent using aqueous solutions of base. The ethylating agent used in reaction of step (a) is Selected from the group comprising diethyl sulphate, ethyl bromide, ethyl chloride preferably diethyl sulphate. The base used in step (a) is selected from the group consisting of potassium hydroxide and sodium hydroxide preferably potassium hydroxide. The suitable solvent used in step (a) is selected from the group of toluene, cyclohexane, xylene, chlorobenzene preferably toluene. The halogenating agent used in reaction of step (b) is selected from the group consisting of aqueous hydrobromic acid, hydrogen bromide in chlorobenzene, hydrogen bromide in carbontetrachloride, hydrogen bromide in dichloroethane, and hydrogen bromide in cyclohexane, hydrochloric acid, hydrogen chloride gas, sulphuryl chloride preferably aqueous hydrobromic acid. The catalyst used in step (b) is selected from the group comprising benzoyl peroxide, Azoisobutyronitrile (AIBN), 2,2'-azobis (2,4-dimethylvaleronitrile), preferably AIBN. The suitable solvents used in step (b) is selected from the group comprising carbon tetrachloride, chlorobenzene., cyclohexane, dichloroethane, preferably carbon tetrachloride. The phase transfer catalyst used in cyanation reaction of step (c) is selected from a group comprising benzyltriethylammonium chloride (BTAC), Benzyltributylammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium chloride, preferably benzyltriethylammonium chloride. The suitable solvent used in step (c) is selected from the group consisting of chlorinated hydrocarbons, alcohols, hydrocarbons preferably ethylene dichloride. The cyanation reaction of step (c) is carried out at temperature ranges from 35 °C to 75 °C preferably 75°C for a time period ranges from 2 to 10 hour preferably 2 hour. The acid used for converting compound of formula (III) to diester compound of formula (IV) in step (d) is selected from the group consisting dry hydrogen chloride gas or concentrated sulphuric acid or combination of sulphuric acid and dry hydrochloric gas and organic solvent used is ethanol. The base used for neutralizing the resultant reaction mass in step (e) from the above reaction is selected from the group comprising of ammonia gas, ammonium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bi carbonate, potassium carbonate, tertiary amines like triethyl amine, preferably ammonia gas. The compound (IV) in neutral solution of ethanol is hydrolyzed by dropwise addition of 8-10% solution of the base at temperature ranges from 15-30°C preferably 20-25°C in 2 hour. The solvent is distilled out and water is added to the resultant reaction mass. The separated aqueous layer is extracted with ethylene dichloride to remove the impurities. Further, the desired compound of formula (V) is recovered from an aqueous medium at an acidic pH 3 using 15 % hydrochloric acid. The base used for hydrolyzing the compound (IV) in step (f) is selected from the group consisting of sodium hydroxide and potassium hydroxide preferably sodium hydroxide. The process of present invention for preparation of 3-Ethoxy-(4-ethoxy carbonyl) phenyl acetic acid is schematically represented as Scheme I. In another embodiment of the present invention the7 compound of formula (V) can be prepared by converting 4-Methyl salicylic acid of formula (VII) into it's aqueous dipotassium salt and further converting the aqueous solution of dipotassium salt of 4-Methyl salicylic acid into fine, free flowing powder of dipotassium salt of compound of formula (VII) using spray drying technique thereby increasing the surface area of reactants and accelerating the rate of reaction and reducing the time of reaction. The process to prepare compound of formula (V) from free flowing powder of dipotassium salt of 4-methyl salicylic acid comprises reacting the dipotassium salt with diethyl sulphate in presence of suitable solvent such as toluene at temperature ranges from 50 -150 °C preferably 105-110 °C and time period of 2 hour. Further the reaction mixture is cooled to 30°C and water is added. The separated aqueous layer is discarded and organic layer is washed with water to remove the salt impurities. The solvent is then distilled out under vaccum to obtain ethyl-2-ethoxy-4-methylbenzoate with quantitative yield of formula (I). The halogenation of the resulted compound (I) from the dipotasium salt consist of combination of different varying concentrations of aqueous hydrobromic acid or hydrochloric acid or sulphuryl chloride, between 5% to 48% (w/w %); preferably 47% (w/w %); and hydrogen peroxide of different varying concentrations between 6% to 50 %(w/w%) preferably 45%(w/w) The process of the present invention is described herein below with reference to the following examples, which are illustrative and should not be construed as limiting the scope of the present invention in any manner. Example 1: Preparation of Ethyl-2-ethoxy-4-methyl benzoate (I) Method (A) 4-methyl salicylic acid (4kg, 2.63 kmole) was added in toluene (52 lit.) and heated to 100 -110 °C. A commercially available caustic potash of 85% purity (3.99 Kg 6.04 kmole)was added to 2.45 lit. water to make a slurry. The caustic potash slurry was added to reaction mass containing 4-methylsalicylic acids in 2 hour at 105°C. During the addition simultaneously water of reaction was removed by azeotropic distillation. On completion of dehydration, 8.5 kg diethylsulphate (5.51 kmole) was added in 1 hour to the reaction mass maintaining the temperature 100 °C The reaction mass was cooled to 30 °C and 10 lit. water was added . The reaction mass was stirred for 0.5 hour.separated aqueous layer was removed and the organic layer was washed with 10 lit. of water. Toluene was distilled (94% recovery of theory) to afford ethyl-2-ethoxy-4-methylbenzoate 5460 gm (quantitative yield). Method (B) A dipotassium salt of 4-methyl salicylic acid (6 kg, 2.63 kmole) was added in toluene and heated to 100-110 °C. 8.5 Kg diethyl sulphate (5.51 kmole) was added to the above solution in 1 hour maintaining the temperature of the reaction mass at ,100 °C for 4 hour. The reaction mass was cooled to 30 °C and 10 lit. water was added to the reaction mass, the reaction mass was stirred for 0.5 hour, two layers separated. The aqueous layer was removed and the organic layer was washed with 10 lit. of water .Toluene was distilled to (95 % recovery of theory) afford ethyl-2-ethoxy-4-methylbenzoate 5400 gm (quantitative yield). Example 2: Preparation of Ethyl-4-halo methyl-2-ethoxy benzoate (II) Method (A) Preparation of Ethyl-4-bromomethyl-2-ethoxy benzoate 50 gm (0.237 mole) compound of formula (I) was dissolved in 150 ml of carbon tetrachloride in 1 lit. four neck round bottom flask with overhead stirrer. 3.9 g azoisobutyronitrile (AIBN) and 36 gm of hydrobromic acid (47 %,w/w) were added to the above solution and refluxed the mass at temperature 70 -75 °C. 49 gm of hydrogen peroxide (45%, w/w) was then added to the reaction mixture in l hour and stirred the mass for further 2h. The separated organic layer was concentrated by distillation of carbon tetrachloride. The reaction mass was cooled at 15-20 °C and the solid of the titled compound was filtered and dried. The yield is 34 gm (50%) Method (B) Preparation of Ethyl-4-chloromethyl-2-ethoxy benzoate 50 gm (0.237 mole) compound of formula (I) was mixed in 150 ml of carbon tetrachloride in 500 ml four neck round bottom flask fitted with overhead stirrer and 1 g benzoyl peroxide was added to the reaction mass.the mass was refluxed gently for l hour and cooled the reaction mass to room temperature , washed with saturated sodium bicarbonate solution. The solvent is removed by distillation to isolate the product. The yield is 25 g (43%). Example 3: Preparation of Ethyl-4-cyanomethyl-2-ethoxy benzoate (III) 0.278 mole of compound of formula (II) was dissolved in 700 ml of ethylene dichloride in 1 lit. reactor with overhead stirrer, 100 ml of water and 7.79 gm of benzyl triethyl ammonium chloride was added to the above solution. A solution of 20 gm of sodium cyanide dissolved in 100 ml water was added to the reactor. The reaction mixture was heated to reflux under stirring for 3h. After completion of reaction two layers separates . out. The organic phase was washed with water. (100 ml x3) and the solvent was distilled out. The reaction mass was cooled under stirring to 20-25 °C. The solid of formula (III) was filtered out to suck dry. The yield is 56 gm (85% yield). Example 4: Preparation of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid (V) Method (A) In a 5 lit. four neck round bottom flask fitted with overhead stirrer, 1637 gm of compound of formula (III) and 4913 ml of anhydrous ethanol was added. The reaction mass was heated to reflux temperature under stirring. Under this condition, Dry HC1 gas was purged in to round bottom flask for 10 hours. After completion of reaction; the reaction mass was cooled and the alcoholic solution was neutralized by purging ammonia gas. The solid ammonium chloride was filtered and the anhydrous ethanol was recovered for further reuses. The yield of compound of formula (IV) is 1770 gm (90%). In a 5 lit. flask containing 1770 gm of compound of formula (IV), 7 liter of absolute alcohol was added and the reaction mass was stirred at 15 -20 °C ,61it. of 8-10 % solution of sodium hydroxide was added dropwise in 2 hours to the above solution stirred further for 2 hours at 25-30 °C. Ethanol was distilled out and 51it. of water was added to the reaction mass. The aqueous layer was extracted with 21it. of ethylene dichloride and 15% hydrochloric acid was added to the aqueous layer till to obtain the pH 3. The solid separated was filtered and dried at 50°C. Yield of compound (V) is 955 gm.(60%). The overall yield from compound (III) to Compound (V) is 54%. Method (B) 5 lit. four neck round bottom flask fitted with overhead stirrer placed with 1637 gm of compound of formula (III), 4913 ml of anhydrous ethanol and 160 gm of concentrated sulphuric acid was added and the reaction mass was heated to 60-80 °C temperature under stirring for 20 hour. After completion of the reaction, the reaction mass was cooled and neutralized by purging ammonia gas. The mixture of solid ammonium sulphate and ammonium chloride was filtered. Anhydrous ethanol was recovered for further reuse. The yield is 1700 gm (86%). In a 5 lit. flask 1700 gm of compound of formula (IV) was taken and 6.8 liter of absolute alcohol was added. The reaction mass was stirred at 15 -20 °C and 61it. of 8-10 % solution of sodium hydroxide solution was added dropwise in 2 hour to the solution, the reaction mixture for further stirred for 2 hour at 25-30 °C and ethanol was distilled out.51it. of water was added to the reaction mass. The separated aqueous layer was extracted with 21it. of ethylene dichloride. The pH of the aqueous layer was adjusted to 3 using 15% hydrochloric acid. The solid separated was filtered and dried at 50°C. Yield of compound (V) is 914 gm.(60%). The over all yield of compound (V) from Compound (III) is 51.6% Method (C) In a 5 lit. four neck round bottom flask fitted with overhead stirrer, 1637 gm of compound of formula (III) was taken and 4913 ml of anhydrous ethanol was added . The reaction mass was heated to reflux temperature under stirring. Under these conditions, dry HC1 gas was purged for 10 hour. The reaction mass was cooled and the alcoholic solution was neutralized by purging ammonia gas. The solid of ammonium chloride was filtered and 1.5 liter recovered alcohol was added to this reaction mass. 6 lit. of 8-10 % solution of sodium hydroxide solution was added dropwise in 2 hours to the above reaction mixture and stirred further for 2 hours at 25-30 °C. Ethanol was distilled out and 5 lit. of water was added to resultant reaction mass and the separated aqueous layer was extracted with 21it. of ethylene dichloride. 15% hydrochloric acid was added to obtain the pH 3 of the aqueous layer. The separated solid was filtered and dried at 50°C. Yield of compound (V) is 1150 gm (65%). Method (D) In a 5 lit. four neck round bottom flask fitted with overhead stirrer, 1637 gm of compound of formula (III) was taken ,4913 ml of anhydrous ethanol and 160 gm of concentrated sulphuric acid was added. The reaction mass was then heated to reflux temperature under stirring for 20 hour. After completion of the reaction, ammonia gas was purged to neutralize the alcoholic solution. The mixture of solid ammonium sulphate and ammonium chloride was filtered and 1.5 liter of recovered ethanol was added to the reaction mass. 6 lit. of 8-10 % solution of sodium hydroxide solution was added dropwise in 2 hours to the above reaction mixture and stirred further for 2 hours at 25-30 °C. Ethanol was distilled out and 5 lit. of water was added. The separated aqueous layer was extracted with 21it. of ethylene dichloride and 15% hydrochloric acid was added to the aqueous layer till to obtain the pH 3. The precipitated solid was filtered and dried at 50°C. The overall yield of compound (V) from compound (III) is 938 gm (53 %). Industrial applicability: 1) The step (a) for producing compound of formula (I) is completed in 7 to 8 hours as compared to 20 -30 hours mentioned in the prior art process. 2) In step (b) for producing compound of fomula (II), hydrobromic acid, hydrochloric acid and sulphuryl chloride are used as a halogenating agent with hydrogen peroxide which a cheaper raw material, making the process cost effective and easy for scale up in plant. Further the run away conditions as disclosed in prior art are totally eliminated. Use of sulphuryl chloride as halogenating agent improves space yield of the product during scale up due to low reaction volumes. 3) Step (c) for producing compound of formula (III) is performed in 3 hour as compared to 25-35 hour as in prior art. 4) Further a cheaper phase transfer catalyst and a low volatile solvent such as ethylene dichloride is used as against methylene dichloride in prior art for easy recovery of the solvent which makes the process cost effective. 5) Ethylene dichloride is used as extracting solvent for removal of impurities in step-(g), which avoids the use of toluene as co solvent for further purification as in the prior art. 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 this invention, which is to be limited only by the scope of the appended claims. We claim, 1. A process for the preparation of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid of formula (V) comprising the steps of: a) reacting 4-methyl salicylic acid of formula (VII) or potassium salt of formula (VII) with diethyl sulphate using base in suitable solvent to obtain compound of formula I; b) halogenating the compound of formula (I) with suitable halogenating agent in presence of hydrogen peroxide and a catalyst in carbon tetrachloride as solvent at temperature range from 30 °C to 75 °C preferably 75°C to obtain ethyl-4-halomethyl-2-ethoxybenzoate of formula (II); c) cyanating the compound of formula (II) with sodium cyanide in the presence of a phase transfer catalyst in suitable solvent system to obtain ethyl-4-cyanomethyl-2-ethoxybenzoate of formula (III); d) treating the compound of formula (III) with an acid as catalyst in presence of ethanol; e) neutralizing the resultant reaction mass of step (d) using base to obtain diester of formula (IV); f) hydrolyzing compound of formula (IV) with 8-10% solution of inorganic base such as sodium hydroxide and potassium hydroxide preferably sodium hydroxide at temperature ranges from 15-30°C preferably 20-25°C in a period of 2 hour and g) isolating 3-ethoxy-4-(ethoxycarbonyl)- phenyl acetic acid of formula (V) by extracting with suitable solvent and conventional acidification technique. 2. The process as claimed in claim 1 wherein, the said dipotassium salt of 4-metyl salicylic acid is prepared by spray drying technique to increase the surface area which in turn increases rate of reaction and reduces time of reaction. 3. The process as claimed in claim 1 wherein, the base used in step (a) is selected from the group consisting of alkali hydroxides preferably potassium hydroxide being a strong base reduces the time of reaction. 4. The process as claimed in claim 1 wherein, the halogenating agent used in step (b) is selected from the group consisting of aqueous hydrogen bromide, hydrogen bromide in chlorobenzene, hydrogen bromide in carbontetrachloride, hydrogen bromide in dichloroethane , hydrogen bromide in cyclohexane, hydrochloric acid, hydrogen chloride gas, sulphuryl chloride preferably aqueous hydrogen bromide. 5. The process as claimed in claim 1 wherein, the catalyst used in step (b) is selected from the group comprising benzoyl peroxide, Azoisobutyronitrile (AIBN), 2, 2'-azobis (2,4-dimethylvaleronitrile), preferably Azoisobutyronitrile (AIBN). 6. The process as claimed in claim 1 wherein the phase transfer catalyst used in step (c) is selected from benzyltriethylammonium chloride (BTAC), Benzyltributylammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium chloride, preferably benzyltriethylammonium chloride. 7. The process as claimed in claim 1 wherein the suitable solvent used in step (c) is selected from the group consisting of chlorinated hydrocarbons, alcohols, hydrocarbons preferably ethylene dichloride. 8. The process as claimed in claim 1 wherein the said reaction in step (c) is carried out at temperature ranges from 35 to 75 °C preferably 75 °C for a time period ranges from 2 to 10 hour preferably 2 hours. 9. The process as claimed in claim 1 wherein the said base used in step (e) is selected from the group comprising ammonia gas, ammonium hydroxide, sodium hydroxide, potassium hydroxide, sodium /carbonate, sodium bi carbonate, potassium carbonate, tertiary amines like triethyl amine, preferably ammonia gas. 10. The process for preparation of 3-Ethoxy-4-(ethoxy carbonyl)-phenyl acetic acid of formula (V) as substantially described herein with reference to the forgoing examples 1 to 4. Dated this 12th day of September, 2006. Dr. Gopakumar G. Nair Agent for the Applicant

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