A PROCESS TO MANUFACTURE PURE ANHYDROUS EPROSARTAN
MESYLATE
FIELD OF THE INVENTION
The present invention relates to a process for commercial manufacture of Eprosartan and its pharmaceutically acceptable acid addition salts thereof in high purity and high yield.
BACKGROUND OF THE INVENTION
Eprosartan, chemically known as (E)-3-[2-Butyl-l-{(4-carboxyphenyl)methyl}-lH-imidazole-5-yl]-2-(thiophen-2-ylmethyl)prop-2-enoic acid is represented by structural formula I. Eprosartan is known to be angiotensin II receptor antagonist, useful in regulating hypertension induced by angiotensin II and useful in the treatment of congestive heart failure, renal failure and glaucoma.

U.S. Patent No. 5185351 describes a process for preparation of imidazole compounds, particularly the preparation of Eprosartan. The process comprises condensation of pentanamidine with dihydroxyacetone to give a diacetate, which was treated with 4-carboxymethylbenzyl alcohol in the presence of triflic acid anhydride to give 2n-butyl-5-acetoxymethyl-l-(4-carboxyphenyl)-methyl-IH-imidazole. The obtained compound on further oxidation with manganese dioxide and thereafter condensation with

methyl-3-(3-(2-theinyl)-propionate in the presence of n-butyl lithium at -78"C gives an ester which on hydrolysis gives Eprosartan. Eprosartan is further converted to its desired salt form. The form of the product obtained here is anhydrous in nature. The process can be best represented by below Scheme I;
Although the process described here can be used for the preparation of Eprosartan, but it has a few drawbacks. This process uses hazardous reagents such as n-butyl lithium, DBU and triflic acid anhydride. These reagents are not suitable to use at manufacturing scale because of their high cost and safety reasons. The temperature of the reaction needs to be maintained at -78"C which is difficult to achieve and maintain all the time at manufacturing scale. Moreover, the overall yield is also very low about 40%. This patent also describes an alternative process for condensation of 2-n-Butyl-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde and Ethyl-2-carboxy-3-(2-thienyl) propionate, in presence of a base, such as piperidine, in a suitable solvent, such as toluene at a temperature of 80 to 110 C, to give a diester intermediate, which is

further hydrolyzed with a base such as sodium hydroxide to give (E)-3-[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylmethyl)-2-propenoic acid.
US6172237 (hereinafter '237 patent) discloses the condensation of 4-[(2-Butyl-5-
formyl-lH-imidazol-l-yl)methyl]benzoic acid or the bisulfite addition compound of 4-
[(2-Butyl-5-formyl-l-yl-imidazol-l-yl)methy!]benzoic acid and 2-
(Thienylmethyl)propanedioic acid (Scheme II) or 2-(Thienylmethyl)propanedioic acid monoethyl ester (Scheme III) at reflux temperature in toluene under reduced pressure 9-13 inches Hg in presence of piperidine as a catalyst followed by hydrolysis of the intermediate ethyl ester to give Eprosartan which is further converted to its desired salt fonn, best represented by Scheme II shown below, the form of the product obtained here is anhydrous fomi;


The major drawback of these processes is the condensation, which is done at reduced pressure of 9-13 inches Hg. It is very difficuU to maintain reduced pressure all the time at higher scale of production, the reaction is time consuming and when used as potassium or sodium salts, the yield is very low.
We repeated the process described in '237 patent and found that during condensation of 2-n-Butyl-1 [(4-carbomethoxy-phenyl)methyl]- l//-imidazole-5-carboxaldehyde and Ethyl-2-carboxy-3-(2-thienyl) propionate a significant amount of impurities viz. (E)-4-[[2-Butyl-5-(2-carboxyethenyl)-1 H-imidazole-1 -yl]niethyl]-benzoic acid of fonnula VIll, 4-[(2-n-Butyl-5-fonTiyl-l H-imidazole-l-yl)methyl]benzoic acid of formula IX, 4-[(2-n-Butyl-5-hydroxymethyl)-l H-imidazole-l-yl)methyl]benzoic acid of fonnula X etc. form, which are carried forward to the final compound. Controlling these impurities specifically impurity VIII, in Eprosartan mesylate is difficult by single purification and yield will be compromised if purified repeatedly.

The present inventors surprisingly found that these impurities can be controlled either by a purificafion of compound of formula I i.e. after the condensation of 2-n-

Butyl-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde with Ethyl-2-carboxy-3-(2-thienyl) propionate followed by hydrolysis, or by controlling the content of malonic acid & malonic acid esters in Ethyl-2-carboxy-3-(2-thienyl) propionate.
US6458963 discloses regioselective protection of nitrogen of the 2-n-butyl-4-fonnyl-lH-imidazole ring followed by treatment with (2-thienylmethyl)propanedioic acid, mono ethyl ester under reduced pressure. This on further treatment with methyl-4-bromomethyl-benzoate, hydrolysis of the ester and followed by deprotection, gives Eprosartan which is converted to its suitable salt fomi as shown in Scheme IV below:
Scheme IV

Alternatively, US6458963 also discloses another process as in Scheme V where 2-n-butyl-4-fonTiyl-lH-imidazole is first condensed with (2-thienylmethyl) propanedioic acid, mono methyl ester and then the product is regioselectively protected, condensed and deprotected to give Eprosartan which is converted to its suitable salt form.


The drawbacks of the processes given in scheme IV and Scheme V are that there is frequent protection followed by deprotection which leads to lower yield and use of costlier reagents like DBU. Hence it is not preferable at manufacturing scale. Secondly, the condensation is carried out under reduced pressure which is difficult to maintain all the time at higher scale of production.
J. Med. Chem. (1991), 34, 1514-1517 discloses a process for the preparation of Eprosartan in which the condensation of the aldehyde with (2-thienylmethyl) propanedioic acid monomethyl ester is carried out in the presence of piperidine using toluene as solvent wherein the reported yield is only 40%.
It is apparent from most of the prior-art that the condensation of 2-/2-Butyl-l[(4-carbomethoxy-phenyl)methyl]- l//-imidazole-5-carboxaldehyde and Ethyl-2-carboxy-3-(2-thienyl) propionate is usually carried out in a suitable solvent with removal of water either azeotropically or under reduced pressure in presence of a base. In these conditions the moisture is not removed completely. The presence of moisture makes the reaction reversible which leads to low yield and long reaction time. Some of the prior art process

uses the hazardous and costly raw materials like n-butyl lithium, DBU and triflic acid anhydride, low temperature like below -78 "C which is difficult to maintain at commercial production level. Some of the prior art uses multiple steps of protection and deprotection which (idds to the cost of production. Therefore, there is a continued need for developing a new process for the preparation of Eprosartan in which moisture can be eliminated completely.
Wc found that if the condensation of 2-«-Rutyl-l [(4-carbomcthoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde and alkyl-2-carboxy-3-(2-thienyl) propionate is done in presence of a water absorbing agent. The reaction moves very smoothly in forward direction towards the completion, which enhances the yield and purity of the reaction.
SUMMARY OF THE INVENTION The present invention provides a process for the commercial manufacturing of Eprosartan of formula I and its pharmaceutically acceptable salt. The process comprises the steps of
(a) reacting 2n-butyl-4-chloro-5-fonTiyl-lH-imidazole of Formula II with methyl-4-(bromo methyl)benzoate of Fonnula III to give 2n-butyl-4-chloro-l[(4-carbomethoxy-phenyl)methyl]-1 Pl-imidazolc-5-carboxaldchyde of fonnula IV;
(b) dehalogenating 2n-butyl-4-chloro-1 [(4-carbomethoxy-phenyl)methyl]-1H-imidazole-5-carboxaldehyde to give 2-«-butyl-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde of fonnula V;
(c) condensation of 2-«-butyl-I[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde with alkyl-2-carboxy-3-(2-thienyl) propionate of Formula VI in presence of a water absorbing agent followed by hydrolysis to give (E)-3-[2-butyl-I-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylmethyl)-2-propenoic acid of Formula I;
(d) optionally, converting the obtained Eprosartan of formula I to its methanesulfonate salt in a suitable organic solvent to give anhydrous Eprosartan mesylate of Formula VII and fUrther purifying with acetic acid.

DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides a process for commercial manufacturing of Eprosartan, chemically known as (E)-3-[2-Butyl-l-{(4-carboxyphenyl) methyl}-lH-imidazole-5-yl]-2-(thiophen-2-ylmethyl)prop-2-enoic acid of Formula I and its conversion to the substantially pure pharmaceutically acceptable acid addition salts, solvates and polymorphs thereof
In an embodiment of the invention, the reaction of the 2-n-butyl-4-chloro-5-fonnyl-lH-imidazole with methyl-4-(bromomethyl)benzoate can be carried out in an organic solvent selected from N,N-DimethylfonTiamide, DMSO preferably N,N-Dimethylfonnamide; in presence of a suitable base selected from alkali metal carbonates preferably sodium carbonate or potassium carbonate, most preferably potassium carbonate to give a compound of formula IV.
In another embodiment of the invention, the dehalogenation of the compound of Formula IV obtained in step (a) is carried out under reduced pressure in presence of palladium-carbon or Raney Nickel in an organic solvent selected from methanol, ethanol or ethyl acetate; preferably in methanol to give a compound of Fonnula V.
In still another embodiment of the invention, 2-«-butyl-l[(4-carbomethoxy-phenyl)mcthyl]-l//-imidazolc-5-carboxaklehydc obtained in step (b) is condensed with alkyl-2-carboxy-3-(2-thienyl) propionate of Formula VI in the presence of a water absorbing agent, which is molecular sieves. This condensation is carried out in presence of a suitable base selected from the group consisting of piperidine, piperidine hydrochloride, morpholine, N-methyl pyrrolidine; preferably in presence of piperidine in an organic solvent selected from group consisting of diisopropyl ether, toluene, cyclohexane, and hexane; preferably in presence of diisopropyl ether. The alkyl-2-carboxy-3-(2-thienyl) propionate of Fomiula VI is selected from methyl-2-carboxy-3-(2-thienyl) propionate, ethyl-2-carboxy-3-(2-thienyl) propionate or propyl-2-carboxy-3-(2-thienyl) propionate, preferably ethyl-2-carboxy-3-(2-thienyl) propionate. The obtained condensed product was hydrolysed in situ in an organic solvent selected from a group consisting of methanol, ethanol or isopropyl alcohol; preferably in methanol using a

suitable base selected from sodium hydroxide or potassium hydroxide most preferably sodium hydroxide.
In still another embodiment of the invention, after completion of hydrolysis the reaction mass was purified by acidification with suitable acid selected from acetic acid or dilute hydrochloric acid; preferably by dilute hydrochloric acid in an organic solvent selected from diisopropyl ether, methanol & isopropyl alcohol, preferably isopropylalcohol to give Eprosartan of Formula 1.
In yet another embodiment of the invention, the obtained Eprosartan of formula I is converted to its pharmaceutically acceptable acid addition salt. The preferable pharmaceutically acceptable acid addition salts of Eprosartan are obtained from, but not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, methanesulfonic acid, benzenesulfonic acid, maleic acid, fijmaric acid, benzoic acid, ascorbic acid, succinic acid and more preferably from methane sulphonic acid. Eprosartan methane sulphonic acid salt of formula VII are obtained by using methane sulphonic acid in an organic solvent selected fonn acetic acid, isopropanol or ethanol; most preferably acetic acid and the anti-solvent used to precipitate the compound is isopropyl acetate.
The solvent used for the purification of the crude Eprosartan mesylate is acetic acid, ethanol or methanol most preferably acetic acid.
The present invention also provides a phannaceutically acceptable active ingredient which is substantially pure with a purity level of 99.85% and impurity level of less than 0.10%.
The obtained Eprosartan mesylate of formula VII is characterised by the major X-ray powder diffraction peaks at 7.2736, 7.7315, 8.0844, 10.6690, 11.1849, 11.7468, 12.6472, 13.1547, 13.3130, 13.6151, 14.0579, 14.4567, 14.5761, 15.4841, 15.6107, 16.2062, 16.8204, 18.4992, 19.0705, 19.7204, 20.2524, 20.5424, 20.8496, 21.1447, 21.4167, 21.6910, 21.9035, 22.4154, 22.6507, 23.4876, 23.7068, 24.4171, 24.5857, 24.8810, 25.2005, 26.0825, 26.5441, 26.9094, 27.2714, 27.9233, 28.3427, 28.7987, 29.0936, 29.8192, 30.5702, 31.3205, 31.7950, 32.1100, 32.8803, 33.1899, 34.2724,

34.5815, 36.0398, 36.9075, 37.1807, 37.9685, 38.4357, 39.3294, 39.6510, 40.2486, 40.6245, 41.7089, 43.3203, 44.2275, 44.9917, 45.8828, 47.8547, 48.6529 at 2? values. The powder x-ray diffraction pattern set out herein was obtained using a PAN Alytical Xpert Pro, equipped with a wide range goniometer using copper Ka radiation source of wavelength, ?=1.541 A. The diffraction pattern is provided in Fig. 1 and the complete set of 2? values, interplaner d-spacings and relative intensities of it are provided in Table
In yet another embodiment of the present invention, there is provided a process for the preparation of Eprosartan Mesylate which is substantially free from (E)-4-[[2-butyl-5-(2-carboxyethenyl)-lH-imidazole-l-yl]methyl]-benzoic acid of formula VIll
In yet another embodiment of the present invention, there is provided a process for the preparation of Eprosartan Mesylate which is substantially free from 4-[(2-n-butyl-5-formyl-lH-imidazole-l-yl)methyl]benzoic acid of formula IX
In yet another embodiment of the present invention, there is provided a process for the preparation of Eprosartan Mesylate which is substantially free from 4-[(2-n-butyl-5-hydroxymethyl)-lH-imidazole-l-yl)methyl]benzoic acid of formula X.
The term "substantially free" of an impurity refers lo Eprosartan mesylate containing less than about 0.15% by weight of the corresponding impurity, more specifically the impurities are less than about 0.1% by weight.
The invention is illustrated by the following examples which are not intended to limit the scope of this invention as defined herein above and as claimed herein below.
EXAMPLES
Example 1: Preparation of 2-Butyl-4-chloro-l[(carbomethoxy-phenyl)methyl]-IH-imidazole-5-carboxaldehyde of formula IV

2-«-Butyl-4-chloro-5-fonnyl-l//-imidazole (100 g) was dissolved in N,N-dimethylformamide (4 vol.) in a four neck round bottom flask and anhydrous potassium carbonate (55.4 g) was added into it. The content was stirred at 25- 30 °C and cooled to 0-5 °C. Methyl-4-(bromomethyl) benzoate (129.2 g) was charged into the reaction mass at 0-5 °C in lots over a period. After completion of the reaction, the reaction mass was quenched in water and stirred for 1 hr at 25-30 °C. The product was filtered, washed with water and dried in air oven at 50-55 °C. The obtained crude product was dissolved in 165 ml of methanol at 50-55 °C, water (330 ml) was charged into the reacfion mass at 50-55 °C. The content was cooled to 20-25 °C and maintained for 2 hrs at 20-25 °C. The product was filtered, washed with methanol ( 165 ml) and dried at 50-55 °C in air oven till moisture content is not more than 1.0 % to give 2n-butyl-4-chloro-l[(4-carbomethoxy-phenyl)iTiethyl]-1 H-imidazole-5-carboxaldehyde. (Dry wt. 16.34 g, Yield = 90.13 %).
Example 2: Preparation of 2-Butyl-l-[(4-carbomethoxy-phenyl)methyl]-IH-imidazole-5-carboxaldehyde of formula V
2-A2-Butyl-4-chloro-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde(100 g) and methanol(1000 ml) was taken into an autoclave, potassium acetate (35.2 g) and 5% palladium on carbon (lOg) was charged under nitrogen atmosphere. The reaction mixture was stirred under hydrogen pressure of 2.8-3.0 Kg/cm" till the completion of reaction. The reaction mass was filtered through celite bed and washed with methanol. The solvent methanol was distilled off under reduced pressure below 45 °C to give the residue. The residue was portioned between ethyl acetate (600 ml) & water (600 ml) and the pH of the mass was adjusted to 8.0-9.0 using sodium carbonate solution at 25-30 °C. The organic layer was separated and the solvent was distilled off under vacuum at below 50 °C. The product was slurried in diisopropyl ether (45 ml) and hexane (90 ml) at 40-45 "C. The contents was cooled to 25-28 °C and stirred for 2 hrs at 25-28 °C. The product and filtered, washed with hexane and dried under vacuum at 40-45°C till LOD is Not more than 0.50% to give 2-«-Butyl-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde. (Dry wt. 72.41, Yield = 80.71 %)

Example 3: Preparation of Eprosartan of formula I.
Diisopropyl ether (125 ml) and piperidine (2.1 g) was charged in RB flask at 25-30 °C. Hydrochloric acid (2.5 ml) was added to it slowly at 25-30 °C. The content was refluxed (65-70 °C) for 3-4 hours. After complete removal of water, the reaction mass was cooled to 50-55 °C followed by addition of molecular sieves (25g) and 2-«-butyl-l[(4-carbomethoxy-phenyl)methyl]-l//-imidazole-5-carboxaldehyde (25g). Ethyl-2-carboxy-3-(2-thienyl) propionate (36g) and piperidine were charged into above reaction mass and the temperature was raised to reflux. The contents were maintained for 20 hours at reflux. After completion of the reaction, the reaction mass was filtered through hytlow bed and distilled under vacuum (600-650 mm of Hg) at temperature below 45 °C and cooled the contents to 25-30 °C. Methanol (75 ml) was added to it followed by sodium hydroxide solution (125 ml). The content was heated to reflux for 3 hrs (65-70 °C). After completion of the reaction, the content was cooled to 35-40 °C and the pH was adjusted to 5.1-5.2 using 10% aqueous hydrochloric acid solution. The content, was cooled to 20-25 °C, maintained for 2 hrs at 20-25 °C, filtered and washed with aqueous isopropyl alcohol followed by water. The wet product was purified in 10% sodium hydroxide solution and isopropyl alcohol to give (E)-3-[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienyli"nethyl)-2-propenoic acid. (Dry wt. 29.5. Yield - 83.68 %).
Example 4: Preparation of Eprosartan mesylate of formula VII (E)-3-[2-Butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylmethyl)-2-propenoic acid (lOOg) and acetic acid (300 ml) were charged into RB flask at 25-30 °C. Methane sulphonic acid (27.2 g) was added to it at 25-30 °C and heated to 65-70 °C to get a clear solution. The content was filtered and the filtrate was charged into another 2 L RB flask and cooled to 40-45 °C. Isopropyl acetate (800 ml) was added to the reaction mass in two equal lots at an interval of 2hrs at 40-45 °C. The reaction mass was cooled to 15- 20 °C, stirred for 4 hrs, filtered the product and washed with isopropyl acetate. The product was suck dried for 30 min and further dried under vacuum (600-650 mm of Hg) at 40-45 °C till LOD is NMT 0.50% to give Monomethanesulfonate saU of (E)-3-

[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylmethyl)-2-propenoic
acid.
(Dry wt. 100 g, Yield = 89.72 %)
Example 5: Purification of Eprosartan mesylate
Monomethanesulfonate salt of (E)-3-[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-
5-yl]2-(2-thienylmethyl)-2-propenoic acid (lOOg) and acetic acid (200 ml) were heated
to 80-85 "C in RB flask and stirred to dissolve. The reaction mass cooled slowly over a
time to 25-30 °C, filtered and washed with ethanol (100ml). The product was dried under
vacuum at 40-45 "C till LOD is less than 0.50% w/w to give the monomethanesulfonate
salt of (E)-3-[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylinethyl)-
2-propenoic acid.
(Dry wt. 83.1, Yield = 83.1%)
Example 6: Preparation of Diethyl-2-thienylidene malonate
Acetic acid was added slowly to a mixture of cyclohexane (500 ml) and piperidine (15 g) at 25-30°C. Diethyl malonate (135.67 g, 0.84 mol) and thiophen-2-aldehyde were added to it at 25-30°C. The contents were heated to reflux for 5-7 hours till the completion of reaction. The cyclohexane was distilled out and ethyl acetate (500 ml) was added to the crude residue. The residue was acidified with 10% HCl. The organic layer was separated and 10%) sodium bicarbonate solution was added and stirred for 30 minutes followed by water washing. The organic layer was separated and 10% sodium metabisulfite solufion was added, stirred and the layers were separated. The ethyl acetate was distilled out under vacuum below 50°C to get the product (209.08 g).
Example 6: Preparation of Diethyl (2-thienylmethy I) malonate:
Diethyl-2-thienylidene malonate (lOOg, 0.39mol) obtained above was taken in methanol (500 ml) at 25-30°C and cooled to 0°C. Sodium borohydride (7.42 g, 0.196 mol) was added to it in 5 equal lots at an interval of 10 minutes. After completion of the reaction, the pH was adjusted to 6.0-6.2 with acetic acid (50 ml), under cold conditions. The salt was filtered off and methanol was distilled out from the filtrate. Ethyl acetate (500 ml)

was added to it along with water at 25-30°C and stirred for 15 minutes. The organic layer was separated and 10% vacuum salt (29.4 g) was added and stirred for 15 minutes. The layers were separated; organic layer was dried over sodium sulphate and distilled to get the desired compound (99.0 g).
Example 7: Preparation of2-Carbethoxy-5-(2-thienyl)propanoic acid: Diethyl (2-thienylmethyl)malonate (100 g, 0.39 mol) obtained above was taken in ethanol (300ml) and 10% sodium hydroxide (0.39 mol) solution was added slowly over 1 hour. The contents were stirred for 48 hours at 25-30°C. The solvent was distilled out and water (500 ml) was added to it followed by diisopropyl ether (2 X 1L ). The aqueous layer was separated, acidified to pH 1 using 2N sulfuric acid and methylene chloride was added. The organic layer was separated and washed with water (3 X 1 L), dried over sodium sulfate (100 g), distilled the methylene chloride to get the compound (76 g).

We claim:
I) A process for preparation of Eprosartan, a compound of fonnula I


Where, R=Ci to C3 alkane
in presence of a water absorbing agent followed by hydrolysis to obtain (E)-3-
[2-butyl-l-[(4-carboxyphenyl)methyl]-imidazole-5-yl]2-(2-thienylmethyl)-2-
propenoic acid of fonnula I and optionally converting into a phannaceutically
acceptable acid addition salt, solvates or polymorphs thereof
2) A process according to claim 1, wherein the obtained Eprosartan of formula I is converted to its anhydrous Eprosartan mesylate of fonnula VII using methanesulfonic acid and a suitable organic solvent and further purifying with acetic acid.



4) A process according to claim 1, wherein the water absorbing agent used
molecular sieves.
5) A process according to claim 1, wherein, the condensation is can-ied out in
presence of a base and an organic solvent.
6) A process according to claim 5, wherein the base is selected from the group
consisting of piperidine, morpholine, N-methylpyrrolidine and a salt thereof and
the organic solvent is selected from the group consisting of diisopropyl ether,
cyclohexane, hexane and toluene.
7) A process according to claim 6, wherein the base used is piperidine or piperidine
hydrochloride and solvent is diisopropyl ether.
8) A process according to claim 1, wherein the condensation is carried out at a
temperature between 40°C and reflux temperature of the solvent used.
9) A process according to claim 8, wherein the reaction is carried out at the reflux
temperature of the solvent used.
10) A process according to claim 1, wherein the hydrolysis is carried out in an
organic solvent selected from group consisting of methanol, ethanol or
isopropyl alcohol; and in presence of a suitable base selected from group
consisting of sodium or potassium hydroxide.

11) A process according to claim 9, wherein the hydrolysis is carried out in
presence of methanol and sodium hydroxide.
12) A process according to claim 1, wherein Eprosartan of formula I is further
purified in water and isopropyl alcohol.