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
"IMPROVED PROCESS FOR THE PREPARATION OF TELMISARTAN"
2. Unichem Laboratories Limited, a company registered under the companies act, 1956, having its registered office located at Unichem Bhavan, Prabhat Estate, S. V. Road, Jogeshwari (West), Mumbai - 400 102, Maharastra, India
3. The following specification particularly describes the invention and the manner in which it is to be performed.

IMPROVED PROCESS FOR THE PREPARATION OF TELMISARTAN
TECHNICAL FIELD
The present invention provides an improved process for the synthesis of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[l,1-biphenyl]-2-carboxylic acid that is Telmisartan.
BACKGROUND OF THE INVENTION
Telmisartan chemically known as 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[l,1-biphenyl]-2-carboxylic acid and is known from U.S. patent no. 5,591,762 and is represented by compound of structural formula (I)

Telmisartan is an angiotensin II receptor (typeAT1) antagonist which is suitable for the treatment of high blood pressure and other medical indications as described in EP 502314 Bl. Telmisartan belongs to the group of angiotensin II antagonists, which are being therapeutically used as medicaments for the cardiovascular system, especially to control high blood pressure. A dosage form of Telmisartan was introduced in the market in 1998 by Boehringer Ingelheim under the protected name Micardis This group contains important drugs like Losartan (Cozaar ®), Irbesartan (Avapro®), or Valsartan (Diovan®). However, unlike these substances Telmisartan shows better efficiency even in the last hours of the administration interval.

U.S. patent no. 5,591,762 describes process to prepare Telmisartan which includes,
a) condensation of 2-n-propyl-4-methyl-6-(l'-methylbenzimidazol-2'-yl)benzimidazole compound of the formula (II) with tert-butyl-4'-bromomethyl biphenyl-2-carboxylate compound of the formula(V) in the presence of an acid binding agent (potassium-tert-butoxide) in a solvent or mixture of solvents (dimethyl sulphoxide (DMSO) to obtain t-butyl 4'-[4-methyl-6-(1 -methyl-1 H-benzimidazol-2-yl)-2-n-propyl-1H-benzimidazole-l-yl-methyl]biphenyl-2-carboxylate compound of the formula(VI) (tert. Butyl ester of Telmisartan)
b) hydrolyzing tert. Butyl ester of Telmisartan compound of the formula (VI) with trifluroacetic acid (TFA) in dimethylformamide (DMF) to obtain crude Telmisartan is purified over a silica gel column and crystallized from acetone to obtain Telmisartan compound of the formula (1) 63.9%.

U.S. Patent no. 7,193,089 describes the process to prepare Telmisartan, which includes,
a) reacting 2-n-propyl-4-methyl-6-(l'-methylbenzimidazol-2, -yl)benzimidazoie
compound of the formula (II) with 4'-(bromomethyl)-[l,l'-biphenyl]-2-carbonitrile compound of the formula (III) in presence of solvent or mixture of solvents

(dimethylacetamide), optionally in the presence of an acid -binding agent such as potassium tert-butoxide or potassium hydroxide at a temperature range 0°C to 20°C, to obtain 2-cyano-4'-[2"-n-propyl-4,,-methyl-6"-(l'"-methylbenzimidazol-2'"-yl)benzimidazol-1"-ylmethyl ]biphenyl , cyanotelmisartan compound of the formula (IV).
b) hydrolysis of cyanotelmisartan compound of the formula (IV) is carried out in presence solvent selected form water, an organic solvents or mixture thereof (such as ethylene glycol/water) in presence of an acid or a base at temperature between 140°C to 200°C.
c) distilled off the solvent from reaction mixture and residue is diluted with water and in hydrochloride acid to obtained Telmisartan hydrochloride is further dissolved in acetic acid and then NaOH is added drop wise at 80°C to 90°C and Telmisartan free base is filtered off.
U.S. patent application no. 2006/0264491 describes process for preparation of Telmisartan. which includes, hydrolysis of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[l,1'-biphenyl]-2-carboxamide compound of the formula (V) in presence of potassium hydroxide in propylene glycol at temperature at about 150°C.

EP2277866 Al discloses a process for preparing Telmisartan from 2-cyano-4;-[2"-n-propyl-4"-methyl-6"-(1"-methylbenzimidazol-2"'-yl) benzimidazol-l"-yl methyl] biphenyl compound of the formula (IV) using 60% NaOH in n-butanol in presence of phase transfer catalyst i.e. tetra butyl ammonium hydrogen sulphate at 115-120°C for 22
h.

EP2443094B1/WO2010/146187A2 describes a process for the synthesis of Telmisartan from cyano Telmisartan and carboxamido telmisartan using 1:1 sulphuric acid at 125°C for 30 h and 28 h respectively.
The existing process requires very high temperature for 30 h or 28 h which limits its large scale application and invites safety risks too. In addition to this, formation of different kind of impurities takes place at 125°C.
Chinese patent application CN 1412183A describes the process for preparation of Telmisartan which includes reacting compound of the formula (II) with compound of the formula (111) in presence of organic base or inorganic base and reaction solvent to afford compound of the formula (IV). It also describes different hydrolysis conditions for compound of the formula (IV) such as,
a. a 1:2 volume ration of concentrated acetic acid: concentrated hydrochloric
acid refluxed for 24 hours at about 100°C
b. a 2:1 volume ration of ethanol: 2 M NaOH refluxed for 24 hours at about
100°C
c. a 1: 1.5 volume ration of sodium ethanolate in glycol: water refluxed for 24
hours and finally obtained Telmisartan is crystallization with N, N-
dimethylformamide (DMF).
Chinese patent application CN102070534A discloses a process for preparation of 2-cyano-4'-[2"-n-propyl-4"-methyl-6"-(1"-methylbenzimidazol-2'"-yl) benzimidazol-1"-ylmethyl ]biphenyl compound of the formula (IV) which includes reacting compound of the formula (II) with compound of the formula (III) under the effect of phase transfer catalyst and inorganic base in the presence of low boiling organic solvents at temperature rang in between 0°C-10oC.
WO 2007/147889 discloses the process for preparation of Telmisartan by hydrolyzing compound of the formula (IV) by addition of water and conc. HC1 heated at reflux

temperature for 136 hours and then cooled reaction mixture at room temperature and add 1M NaOH to adjust pH to about 5 to 7. The product is filtered, wash and dried to obtain Telmisartan.
The disclosed process in WO '889 is time intensive besides corrosive and hazardous reaction condition.
U.S. patent no. 5,591,762 teaches the hydrolysis of cyanotelmisartan compound of the formula (IV) using trifluroacetic acid in dimethyl formamide and is not eco-friendly. It involves long time for hydrolysis. Separation of Telmisartan using silica gel column chromatography results into lower yields. Further the preparation of tert. Butyl ester of Telmisartan is relatively expensive method.
U.S. Patent no. 7,193,089 is silent about the purity of the free Telmisartan. The solvents used such as dimethyl acetamide and ethylene glycol have a boiling point greater than about 140°C. These solvents are difficult to remove from the reaction using various evaporation techniques known in the art. These reaction conditions are hazardous and far from being environmental friendly. The process is carried out at very high temperature. Removal of residual solvents from reaction mixture, using various evaporation techniques is tedious and difficult.
U.S. patent application no. 2006/0264491 describes a process in which, an expensive solvent is used. Reactions are carried out at very high temperatures which itself is very difficult to maintain at plant scale manufacturing. These process conditions discourage use of this process.
Process disclosed by EP2277866A1 requires high temperature and longer time to complete the reaction which invites safety risks. Use of lower temperatures substantially impacts on yield. Moreover the isolation procedure from n-butanol to get crude telmisartan is very tedious.

Process disclosed by WO 2010/146187A2 requires very high temperature for longer durations. It limits its application for large scale production. It also invites safety risks. The process leads to formation of different kind of impurities at 125°C. Carrying out reaction at elevated temperatures is not easy and not advisable. Use of lower temperatures substantially impacts yield.
Chinese patent application CN1412183A describes conditions that required long time for hydrolysis and results in lower yields. Moreover ethylene glycol and DMF are high boiling solvent so it will be very difficult to recover and reuse.
CN102070534A teaches a reaction which is carried out at a temperature range of 0-10°C, a range which is difficult and energy intensive. Industry will welcome a reaction which is carried out at ambient temperatures and yet having shorter durations. Besides this inconvenient temperature range the reaction necessitates low boiling solvents and thereby restricts selection range of solvents.
Therefore the processes taught by prior patents and prior art disclosures have several drawback's namely expensive nature, not suitable for scale up at plant level, energy intensive, difficult, giving lower yields, forcing use of corrosive acids, longer duration of corrosive reaction and less user friendly.
Therefore industry strongly needs a process that is simpler, financially cheaper and energy economic process, an environment friendly process that does not use hygroscopic and pyrophoric chemicals. Industry needs a process to produce Telmisartan that can be carried out at lower temperatures yet giving good yields, a process that has improved carbon efficiency and is free from hazards and draw backs of prior art.
OBJECT OF THE INVENTION
The main object of the present invention is to provide a simpler process to prepare Telmisartan.

Another object of the invention is to provide a cost effective, environment friendly and energy economic process to prepare Telmisartan.
Yet another object of the invention is to provide a process to prepare Telmisartan that has good yield and improved carbon efficiency.
SUMMARY OF THE INVENTION:
According to the first aspect of the present invention is to provide process for the preparation of 4'-[(l,4,-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[l,1'-biphenyl]-2-carboxylic acid, Telmisartan compound of the formula (I) comprising: hydrolyzing compound of the formula (IVa) in acid in presence of alkali metal nitrite at lower temperature and shorter duration.

wherein R' represent cyano or aminocarbonyl group.
optionally isolating and hydrolyzing compound of the formula (IVa) (when R' is aminocarbonyl group) while hydrolyzing compound of the formula (IVa- when R' is cyano) into compound of the formula (I).
Another aspect of the present invention is to provide process for the preparation of compound of the formula (IVa) comprising, condensing 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole compound of the formula (II) with compound of the formula (IIIa) in organic solvent by using phase transfer catalyst (PTC) and an inorganic base in presence of alkali metal iodide


wherein Z represents a leaving group selected from the group consisting of chlorine, bromine, iodine, tosyl. methanesulfonyloxy, ethanesulfonyloxy, butanesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, p-bromobenzenesulfonyloxy, mesitylenesulfonyloxy, acetyloxy, propionyloxy, trifluoroacetyloxy, and benzoyloxy and R' represent cyano or aminocarbonyl group.
Yet another aspect of the present invention is to provide process for the preparation of 4'-
[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[1,l'-biphenyl]-2-
carboxylic acid, Telmisartan compound of the formula (I) comprising: condensing 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl) benzimidazole compound of the formula (II) with compound of the formula (III) in organic solvent by using phase transfer catalyst (PTC) and an in inorganic base in presence of alkali metal iodide to obtain cyanotelmisartan compound of the formula (IV), hydrolyzing cyanotelmisartan compound of the formula (IV) in acid in presence of alkali metal nitrite to obtain Telmisartan compound of the formula (I) according to following scheme I.


As stated in the first paragraph of "Summary of the Invention", the process provides an option to isolate and hydrolyze compound of the formula (IVa) (when R' is aminocarbonyl group) while hydrolyzing compound of the formula (IVa- when R' is cyano) into compound of the formula (I).
DETAILED DESCRIPTION OF THE INVENTION
It was surprisingly observed that rate of the reaction of hydrolysis of the compound of the formula (IVa) is very fast as compared to prior art reported process. Moreover it is also observed that acid hydrolysis as disclosed by present invention takes place at lower temperature in presence of alkali metal nitrite.
The present invention relates to an improved process for the preparation of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-1 H-benzimidazol]-l'-yl)methyl]-[l, 1 '-biphenyl]-2-carboxylic acid, (Telmisartan) compound of the formula (I).
hydrolyzing compound of the formula (IVa) in acid in presence of alkali metal nitrite


wherein R' represent cyano or aminocarbonyl group.
optionally isolating and hydrolyzing compound of the formula (IVa) (when R' is aminocarbonyl group) while hydrolyzing compound of the formula (IVa- when R' is cyano) into compound of the formula(I).
The inventive step of the present invention resides in use of acid mediated hydrolysis at surprisingly different temperature range and different durations. Inventive step also resides in the second step of the reaction where conversion into compound of the formula I is achieved at ambient temperatures in presence of alkali metal nitrite at shorter durations.
The examples of acids may include but not limited to hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, trichloroacetic acid, acetic acid or aqueous solutions thereof or mixture(s) thereof, preferably sulfuric acid.
The hydrolysis of compound of the formula (IVa) is preferably carried out in presence of aqueous acidic condition, preferably 80%, more preferably in 75% sulfuric acid.
It was surprisingly noticed that the conversion of compound IVa to compound I takes place at lower temperatures and in shorter duration. Lower temperatures are to be construed as range of 20°C to 50°C. Shorter duration is to be construed as between 3 Hours to 6 Hours.

The examples of alkali metal nitrite may include but not limited to sodium nitrite, potassium nitrite, calcium nitrite, preferably sodium nitrite. It may be used as an aqueous solution.
The addition of acid during the hydrolysis reaction can be carried out at temperature ranging between 60° C to 130°C, preferably 80°C to 120°C, more preferably between 90°C to 100°C.
The drop wise addition of alkali metal nitrite can be carried out at temperature range in between 20°C to 50°C, more preferably between 45°C to 50°C.
The above hydrolysis is carried out in acidic condition followed by addition of alkali metal nitrite.
After the hydrolysis reaction is over the pH of reaction mixture is adjusted. The pH is adjusted to 10 to 12 by using an inorganic base, preferably sodium hydroxide or ammonium hydroxide preferably 40% sodium hydroxide, followed by extraction with n-butanol.
The oily residue thus obtained after distillation and was dissolved in methanol and ammonia, pH of the reaction mixture is adjusted to 4-5 by using acid such as acetic acid to obtain solid.
The obtained solid is washed with methanol and dried over 60°C to 65°C.
Isolating and hydrolyzing compound of the formula (IVa) (when R' is aminocarbonyl group) while hydrolyzing compound of the formula (IVa-when R' is cyano) into compound of the formula (I) in acid in presence of alkali metal nitrite. Preferably 22%-30% of sulfuric acid.
The preparation of compound of the formula (IVa) involves condensing 2-n-propyl-4-methyl-6-(r-methylbenzimidazol-2'-yl)benzimidazole compound of the formula (II)

with compound of the formula (IIIa) in organic solvent by using phase transfer catalyst (PTC) and an in inorganic base in presence of alkali metal iodide to obtain compound of the formula (IVa).

wherein Z represents a leaving group selected from the group consisting of chlorine, bromine, iodine, tosyl, methanesulfonyloxy, ethanesulfonyloxy, butanesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, p-bromobenzenesulfonyloxy, mesitylenesulfonyloxy, acetyloxy, propionyloxy, trifluoroacetyloxy, and benzoyloxy and R' represent cyano or aminocarbonyl group.
The organic solvents may include but not limited to aromatic solvents, chlorinated solvent, ketone solvent or aqueous solutions thereof or mixture(s) thereof.
The examples of aromatic solvents may include but not limited to toluene, xylenes (ortho, meta, para xylene) or aqueous solutions thereof or mixture(s) thereof.
The examples of chlorinated solvents may include but not limited to methylene chloride, ethylene chloride, mono chloro benzene or aqueous solutions thereof or mixture(s) thereof.
The examples of ketone solvents may include but not limited to methyl ethyl ketone, methyl isobutyl ketone, acetone, cyclohexanone or aqueous solutions thereof or mixture(s) thereof.

The examples of inorganic base may include but not limited to sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate or a combination thereof.
The examples of phase transfer catalysts may include but not limited to crown ether or quaternary ammonium salts, such as tetra butyl ammonium bromide, tetra methyl ammonium bromide, tetra ethyl ammonium bromide, tetra propyl ammonium bromide tetra butyl ammonium chloride, tetra methyl ammonium chloride; tetra ethyl ammonium chloride, tetra propyl ammonium chloride.
Crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups. These ethers are oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., -CH2CH2O-.
It was surprisingly noticed that use of alkali metal iodide enhances the rate of the reaction, in the condensation reaction of compound of the formula (11) and compound of the formula (IIIa).
The examples of alkali metal iodide are selected from group consisting of sodium iodide, potassium iodide, calcium iodide, lithium iodide, Copper Iodide preferably potassium iodide.
The condensation of compound of the formula (II) with compound of the formula (IIIa) is carried out at temperature starting from 10°C to refluxing temperature of the solvent, preferably at 40-50°C for a period of 1 hour to 8 hours.
The solution was then cooled to room temperature and then filtered to obtain residue. The
obtained residue is then washed with water to remove the inorganic salts. The obtained
solid was then dried to get compound of the formula (IVa),
Charcholization is to be construed as addition or treatment with Charcoal.
The drying may be performed according to a conventional method, e.g., drying under
reduced pressure.

The obtained residue may be used as such to next hydrolysis step for the preparation of Telmisartan.
The invention is further illustrated by way of the following examples.
EXAMPLES
EXAMPLE-1:
Preparation of 2-cyano-4,-[2"-n-propyl-4"-methyl-6"-(l"'-methylbenzimidazol-2"'-
yl) benz- imidazol-l"-ylmethyl] biphenyl
2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole (25 gm), Tetra butyl ammonium bromide (1 gm). Potasium hydroxide (9.25 gm), Potassium iodide (0.25 gm), O-xylene (125 ml), water (9.25 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45°C for 1 hr. 4'-(bromomethyl)-[l,r-biphenyl]-2-carbonitrile (24.57 gm) was added to form reaction mixture. The reaction mixture was stirred for about 6-8 h at 45 C. Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to remove inorganic salts. The product obtained was dried to get 39.8 gm (yield 98 %) of compound (IV) having purity >98 % by HPLC.
EXAMPLE-2:
Preparation of 2-cyano-41'-[2"-n-propyl-4"-methyl-6"-(1"-methylbenzimidazol-2"'-yl) benz- imidazol-l"-ylmethyl] biphenyl
2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole (25 gm), Tetra butyl ammonium bromide (1 gm), Sodium hydroxide (6.5 gm), Potassium iodide (0.25 gm), methyl ethyl ketone (MEK) (125 ml), water (6.5 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45 C for 1 hr. 4'-(bromomethyl)-[l,l'-biphenyl]-2-carbonitrile(24.57 gm) was added to form reaction mixture. The reaction mixture was stirred for about 6 hrs at 45°C. Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to

remove inorganic salts. The product obtained was dried to get 26.5 gm (66 %) of compound (IV) having purity >98 % by HPLC.
EXAMPLE-3:
Preparation of 2-cyano-4'-[2"-n-propyl-4"-methyl-6"-(1"-methylbenzimidazol-2"'-yl) benz- imidazol-1"-ylmethyl] biphenyl
2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole (25 gm), Tetra butyl ammonium bromide (1 gm), Sodium hydroxide (6.5 gm), Potassium iodide (0.25 gm), mono chloro benzene (MCB) (125 ml), water (6.5 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45°C for 1 hr. 4'-(bromomethyl)-[l,1'-biphenyl]-2-carbonitrile(24.57 gm) was added to form reaction mixture. The reaction mixture was stirred for about 6 hrs at 45°C. Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to remove inorganic salts. The product obtained was dried to get 26.3 gm (65 %) of compound (IV) having purity >99 % by HPLC.
EXAMPLES:
Preparation of 2-cyano-4'-[2"-n-propy]-4"-methyl-6"-(1"-methylbenzimidazol-2"'-yl) benz- imidazol-l"-ylmethyl] biphenyl
2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yi)benzimidazole (25 gm), Tetra butyl ammonium bromide (I gm), Sodium hydroxide (6.5 gm), Potassium iodide (0.25 gm), Methyl isobutyl ketone (MIBK) (125 ml), water (6.5 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45°C for 1 hr. 4'-(bromomethyl)-[l,l'-biphenyl]-2-carbonitrile(24.57 gm) was added to form reaction mixture. The reaction mixture was stirred for about 6 hrs at 45 C. Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to remove inorganic salts. The product obtained was dried to get 26.3 gm (65 %) of compound (IV) having purity >98 % by HPLC.

EXAMPLE-5
Preparation of 2-cyano-4,-[2"-n-propyl-4"-methyl-6"-(l'''-methylbenzimidazol-2"'-yl) benz- imidazol-l"-ylmethyl] biphcnyl
2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole (150 gm), Tetra butyl ammonium bromide (6.0 gm), Potassium hydroxide (34.5 gm), Potassium iodide (1.5 gm), O-xylene (750 ml),water (34.5 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45°C for 1 hr. 4'-(bromomethyl)-[l,1'-biphenyl]-2-carbonitrile(147.5 gm) was added to form reaction mixture. The reaction mixture was stirred for about 6 hrs at 450C.Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to remove inorganic matter. The product obtained was dried to get 239 gm (98 %) of compound (IV) having purity >98% by HPLC.
EXAMPLE -6:
Preparation of 4'-[2"-n-propyl-4"-methyl-6"-(l",-methyIbenzimidazol-2"'-yl) benz-
imidazol-l"-ylmethyl] biphenyl-2-carboxamide
2-n-propyl-4-methyl-6-(l'-methylbenzimidazol-2'-yl)benzimidazole (150 gm), Tetra butyl ammonium bromide (6.0 gm), Potassium hydroxide (34.5 gm), Potassium iodide (1.5 gm), 0-xylene (750 ml), water (34.5 ml) were added to round bottom flask equipped with stirrer, reflux condenser and water bath. The mixture was heated at 45 C for 1 hr. 4'-(bromomethyl)-[l,1'-biphenyl]-2-carboxamide(157.19 gm) was added to the reaction mixture. The reaction mixture was stirred for about 6 hrs at 45 C. Cooled reaction mass at RT and filtered the product. Finally the solid was washed with water to remove inorganic matter. The product obtained was dried to get 232 gm (91.77 %) of 4'-[2"-n-propyl-4"-methyl-6"-(1'-methylbenzimidazol-2"'-yl) benz- imidazol-1"-ylmethyl] biphenyl-2-carboxamide, having purity >99 % by HPLC.

methylene dichloride (200 mL). After that the aqueous layer was treated with acetic acid to get Telmisartan crude. Solid obtained was filtered, washed with water (100 mL) and dried at 60-65 °C. The solid was then dissolved in methanol (600 mL), ammonia (25 mL) solution and followed by charcholization. The pH of filtrate was adjusted 4.5-5 using acetic acid. The solid thus obtain was then filtered followed by washing with methanol (100 mL) to get pure Telmisartan. The product obtained was dried at 60-65 C to get 72 gm (yield 69.56 %) of compound (I) having purity > 99.7 % by HPLC.
EXAMPLE -9:
Preparation of 4,-[(l,4'-dimethyl-2,-propyl [2,6'-bi-lH-benzimidazol]-r-yl)methyl]-
[l,r-biphenyl]-2-carboxylic acid
100 gm of 2-cyano-4'-[2''-n-propyl-4"-methyl-6"-(r"-methylbenzimidazol-2"'-yl) benz-imidazol-1"-ylmethyl] biphenyl and 550 mL 70% sulfuric acid, were heated to 80°C-85° C. The reaction mixture stirred for 8-10 h at this temperature. Water (500 mL) was added at the same temperature and then the temperature was raised to 120-130 C and stirred for 15-20 h. The reaction was then cooled to 20-25° C and stir for 2 h at same temperature. The solid thus obtain was collected by filtration. The solid was then treated with acetone (700 mL), ammonia (150 mL) solution and stirred at 20-25° C for 2 h. The reaction mixture was then filtered and pH of filtrate was adjusted to 4-5 by adding acetic acid. The solid was then obtained by filtration followed by treatment with water. The aqueous slurry was heated at 50-60° C for 2-3 h. The solid thus obtain was filtered to get pure Telmisartan. The product obtained was then dried at 60-65 °C to get 65 gm (yield 62.5 %) of compound (I) having purity > 99.7 % by HPLC.
EXAMPLE-10: . Preparation of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-l'-yl)niethyl]-[l,l'-biphenyl]-2-carboxylic acid
100 gm of 2-cyano-4'-[2"-n-propyl-4"-methyl-6''-(1'''-methylbenzimidazol-2",-yl) benz-imidazol-l''-ylmethyl] biphenyl and 550 mL 75% sulfuric acid, were heated to 80°C-85° C. The reaction mixture stirred for 8-10 h at this temperature. pH of mixture was adjusted to 8-10 by adding 25% ammonium hydroxide solution. After that 500 mL methylene dichloride were added and separated out the layers. The oily residue thus obtain after

EXAMPLE -7:
Preparation of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-benzimidazol]-l'-yl)methyl]-
(l,1'-biphenyl]-2-carboxylic acid
100 gm of 2-cyano-4'-[2"-n-propyl-4"-methyl-6"-(1"'-methylben2imidazol-2"'-yl) benz-imidazol-1''-ylmethyl] biphenyl and 550 mL 75% sulfuric acid, were heated to 80°C-85° C. The reaction mixture stirred for 8-10 h at this temperature. NaNO2 solution (51.6 gm, 0.7478 mol in 304 ml water) was added drop wise and the temperature of the reaction mass was kept at 25-35 C. The reaction was then heated to 45 C and maintained for 12 h and then cooled to 20-25° C. pH of mixture was adjusted to 12 by adding 40% NaOH solution. After that 500 ml of n-Butanol were added and separated out layers. The oily residue thus obtain after distillation was dissolved in 700 mL of methanol and 15 mL of ammonia followed by charcolization. pH of the filtrate was adjusted to 4-5 using acetic acid. Solid obtained was filtered and washed with methanol (100 mL) and dried at 60-65 °C. The solid was then treated with water (500 mL) at 40-45 °C for 3h to remove inorganic matters and then dried at 60-65 °C for 10 h. The solid thus obtain was treated with methanol (1000 mL) at 60-65 °C for 8-10 h and then filtered to get pure Telmisartan The product obtained was then dried at 60-65 C to get 72 gm (yield 69.56 %) of compound (I) having purity > 99.7 % by HPLC.
The reaction proceeds satisfactorily when mixtures of acids are used such as mixture of sulfuric acid and acetic acid or sulfuric acid and hydrochloric acid.
EXAMPLE -8:
Preparation of 4'-[(l,4'-dimethyl-2'-propyl [2,6'-bi-lH-bcnzimidazol)-r-yI)methyl]-
ll,l'-biphenyll-2-carboxyIic acid
100 gm of 2-cyano-4'-[2"-n-propyl-4"-methyl-6"-(1"-methylbenzimidazol-2'"-yl) benz-imidazol-1''-ylmethyl] biphenyl and 550 mL 80% sulfuric acid, were heated to 80°C-85° C. The reaction mixture stirred for 8-10 h at this temperature. Water (500 mL) was added at the same temperature and the reaction mixture was stirred for 15-20 h and reaction was completed at 120-130 C. The reaction was then cooled to 20-25 C. pH of mixture was adjusted tol2 by adding 40% NaOH solution. After that 500 ml of n-Butanol were added and separated out layers. The oily residue thus obtain after distillation was dissolved in 500 mL of water to get clear solution. The aqueous layer was washed with

distillation of methylene dichloride was added in 300 mL of acetone. Suck dry the wet cake.
Wet cake was directly charged in a reaction assembly containing 900 mL 30% sulfuric acid solution. NaN02 solution (48.75 gm, 0.7 moles in 200 ml water) was added drop wise and the temperature of the reaction mass was kept at 25-50 C. The reaction was then heated to 45°C-50°C and maintained for 2-5 h and then cooled to 20-25° C. pH of mixture was adjusted to 12 by adding 40% NaOH solution. After that 500 ml of n-Butanol were added and separated out layers. The oily residue thus obtain after distillation was dissolved in 700 mL of methanol and 15 mL of ammonia followed by charcolization. pH of the filtrate was adjusted to 4-5 using acetic acid. Solid obtained was filtered and washed with methanol (100 mL) and dried at 60-65 °C. The solid was then treated with water (500 mL) at 40-45 °C for 3h to remove inorganic matters and then dried at 60-65 °C for 10 h. The solid thus obtain was treated with methanol (1000 mL) at 60-65 °C for 8-10 h and then filtered to get pure Telmisartan. The product obtained was then dried at 60-65 °C to get 73 gm (yield 75.9 %) of compound (I) having purity > 99.7 % by HPLC.
Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the said invention, will become apparent to persons skilled in the art upon reference to the description of the invention. It is therefore contemplated that such modifications can be made without departing from the true spirit or scope of the present invention as exemplified and claimed herein below.

We claim:
1. A process for the preparation of 4'-[(l,4-dimethyl-2-propyl [2,6'-bi-lH-benzimidazol]-1'-yl)methyl]-[l,l'-biphenyl]-2-carboxylic acid, Telmisartan compound of the formula (I) comprising :
hydrolyzing compound of the formula (IVa) in acid at temperature range between 60°C to 130°C, preferably between 80°C to 130°C, more preferably between 100°C to 130°C in presence of alkali metal nitrite at temperature range between 20°C to 50°C, more preferably between 45°C to 50°C, to obtain compound of the formula (I)

wherein R' represent cyano or aminocarbonyl group,
optionally isolating and hydrolyzing compound of the formula (IVa) (when R' is aminocarbonyl group) while hydrolyzing compound of the formula (IVa) ( when R' is cyano) into compound of the formula (I) at a temperature range between 20°C to 50°C, more preferably between 45°C to 50°C
2. The process according to claim 1, wherein the acid is selected from group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, trichloroacetic acid, acetic acid or aqueous solutions thereof or mixture(s) thereof.
3. The process according to claim 1, wherein the alkali metal nitrite is selected from group consisting of sodium nitrite, potassium nitrite, calcium nitrite.

4. A process for preparation of compound of the formula (IVa) comprising,
condensing 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)benzimidazole compound of the formula (II) with compound of the formula (IIIa) in organic solvent using phase transfer catalyst (PTC) and an in inorganic base in presence of alkali metal iodide at temperature range between 10°C to 50°C, preferably between 40°C to 50°C for a period of 1 hour to 8 hours.

wherein Z represent leaving group and R' represent cyano or aminocarbonyl group.
5. The process according to claim 4, wherein the organic solvent is selected from the group consisting of toluene, o-xylene, m-xylene, p-xylene, monochlorobenzene, methylene chloride, ethylene chloride, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), acetone, cyclohexanone or aqueous solutions thereof or mixture(s) thereof.
6. The process according to claim 4, wherein the phase transfer catalyst is selected from group consisting of crown ether or quaternary ammonium salts including tetra butyl ammonium bromide, tetra methyl ammonium bromide, tetra ethyl ammonium bromide, tetra propyl ammonium bromide tetra butyl ammonium chloride, tetra methyl ammonium chloride, tetra ethyl ammonium chloride, tetra propyl ammonium chloride.
7. The process according to claim 4, wherein base is selected from group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate or a combination thereof.

8. The process according to claim 4, wherein the alkali metal iodide is selected from group consisting of sodium iodide, potassium iodide, calcium iodide, lithium iodide, copper iodide, preferably potassium iodide.
9. The process according to claim 4, wherein Z represents a leaving group selected from the group consisting of chlorine, bromine, iodine, tosyl, methanesulfonyloxy, ethanesulfonyloxy, butanesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, p-bromobenzenesulfonyloxy, mesitylenesulfonyloxy, acetyloxy, propionyloxy, trifluoroacetyloxy, and benzoyloxy.
10. A process to prepare the compound of the formula (I) comprising hydrolyzing compound of the formula(IV) in acid wherein the acid is hydrochloric acid, sulfuric acid, phosphoric acid, tritluoroacetic acid, trichloroacetic acid, acetic acid or aqueous solutions thereof or mixture(s) thereof, preferable acid being Sulphuric acid; at temperature range between 60°C to 130°C, preferably between 80°C to 130°C, more preferably between 100°C to 130°C in presence of alkali metal nitrite wherein the said nitrite is selected from group consisting of sodium nitrite, potassium nitrite, calcium nitrite preferable being Sodium Nitrite, at temperature range between 20°C to 50°C, more preferably between 45°C to 50°C.