AN IMPROVED PROCESS FOR THE PREPARATION OF 2-BUTYL-3-[[2'-(lH-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL]METHYL]-l,3- DIAZASPIRO [4.4] NON-1-EN-4-ONE POLYMORPHIC FORM A

TECHNICAL FIELD OF THE INVENTION

The present invention is directed to a novel, industrially viable and cost effective process for manufacturing substantially pure form of 2-butyl-3-[[2'-(lH-tetrazol-5-yl)[l,1’-biphenyl]-4yl] methyl] -l,3-diazaspiro[4.4]non-l-en-4-one commonly known as Irbesartan.

BACKGROUND OF THE INVENTION

Irbesartan is an angiotensin 11 receptor antagonist of the formula (I). Irbesartan inhibits the action of angiotensin II on its receptors and thus prevents the increase in blood pressure produced by the hormone -receptor interaction and hence used in the treatment of hypertension and heart failure.

Irbesartan exists in Polymorph Form A, Form B, Form C, hydrate, crystalline and amorphous forms. It is soluble in 96% ethanol.

US5270317 first time disclosed the preparation of Irbesartan generically which comprises the reaction of l-amino cyclopentane nitrile of formula II with acetone and oxalic acid dihydrate to give 1-amino cyclopentane nitrile hemioxalate which gets converted to 1-amino cyclopentane acetamide and on further reaction with valeroyl chloride gives 1 -(N-valeryl)amino cyclopentane carboxamide of formula III, The compound III further reacts with potassium hydroxide, water, methanol and ammonium chloride to give compound IV . Compound IV and compound V undergoes coupling in presence of sodium hydride, dimethylformamide, ethylacetate and water to give compound VI which undergoes azidation and simultaneous cyclization in presence of trityl chloride to give trityl Irbesartan of formula VII.

Scheme I

Compound VII undergoes reaction with methylalcohol, tetrahydrofuran, 4N hydrochloric acid, water and ION sodium hydroxide to give Irbesartan of formula I as in scheme I.

US6162922 describes the process for the preparation of intermediate 4-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-1-ene-3-yl]methyl][1,1-biphenyl]-2-carbonitrile which comprises reaction of hydrochloride salt of formula IV with 4'-(bromomethyl)[1,1-biphenyl]-2-carbonitrile of formula V in presence of water immiscible solvent such as dichloromethane or toluene, base such as sodium hydroxide and potassium hydroxide, phase transfer catalyst such as methyl tributyl ammonium chloride, crystallizing solvent such as methyl tert butyl ether to give compound VI as in scheme II

WO200673376 elucidates the synthesis which involves the reaction of 5-[4-(bromomethyl) biphenyl-2-yl)-l-(triphenylmethyl) tetrazole of formula IV with 2-n-butyl-4-cyclopentane-2-imidazoHn-5-one of formula Va in presence of solvent 1 such as acetonitrile, dimethylsulphoxide, dimethylformamide, dimethyl acetonitrile; phase transfer catalyst such as tetrabutylammonium bromide, 18-crown-6,cryptands, tris(3,6-dioxaheptyl)amine or pyridyl sulphoxide and base such as potassium hydroxide, lithium hydroxide, sodium hydroxide to give trityl Irbesartan of formula. Trityl Irbesartan is deprotected by solvent such as methanol, ethanol, isopropanol, propanol, butanol; base such as sodium hydroxide, potassium hydroxide or lithium hydroxide also alcoholates such as sodium alcoholate, potassium alcoholate, lithium alcoholate followed by the reaction with water, solvent 2 such as methylene chloride, heptane, hexane, toluene, tert-butyl methyl ether; acidified with 2N hydrochloric acid to give crude Irbesartan. Crude Irbesartan is recrystallised from solvent such as methanol, ethanol, isopropanol, propanol, butanol, isobutanol, tert-butanol, dimethylformamide, dimethylsulphoxide, dioxane, tetrahydrofuran, 3-pentanone, 2-butanone, 4-methyl-2-pentanone to give Irbesartan of formula I as in Scheme III.

WO2006023889 setforths the process which comprises 4'-methylbiphenyl-2-carbonitrile of formula VIII which undergoes bromination in presence of bromine and N-bromo succinimide, solvent such as tetrachloro carbon, chloroform, methylene dichloride to give mixtures of compounds ( IX a, IX b, IX c). These compounds undergoes coupling with 2-n-butyl-4-cyclopentane-2-imidazolin-5- one followed by basification and simultaneous reduction to give compound of formula VI. Formula VI undergoes azidation in presence of azylating agents such as sodium azide, triethylamine chlorohydrate, N-methyl pyrrolidinone and sodium hydroxide to give Irbesartan as in scheme IV.

US20070213539 defines the process which comprises the coupling of 4-bromobenzyl bromide with hydrochloride salt of 2-butyl-l,3-diazaspiro[4.4]non-l-ene-4-one to give 2- butyl-3- (4'-bromophenyl)-l,3-diazaspiro[4.4]non-l-ene-4-one of formula Via. 5-phenyl-lH tetrazole gets converted to 5-phenyl-l -trityl-lH tetrazole which further reacts with n-butyl lithium, triisopropyl borate and tetrahydrofuran to give 2-(5-tetrazoyl)phenyl boronic acid of formula X. Compound of formula Via and X couples in the presence of catalyst and solvent to give trityl Irbesartan which is acidified with solvent like acetone and aqueous hydrochloric acid to give Irbesartan as in scheme V.

WO2007052301 describes the process where 2-(n-butyl)-3-oxa-l-azaspiro [4.4] non-l-en-4-one of formula XI couples with 4-aminomethyI-biphenyl derivative in presence of solvent to give compound XII which on cyclization gives an intermediate XIII. The intermediate XIII on azylation in presence of sodium azide or tributyltin azide, solvent such as toluene, xylene, tetrahydrofiiran in case of cyano compound or undergoes (hydrolysis in presence of acid such as hydrochloric acid, sulphuric acid ,phosphoric acid and base (optionally it can also be carried out in alcohol) in case of
tetrazoyl compound to give formula I as in scheme VI.

US20070099973 defines process which starts with the reaction of cyclopentanone which gets converted to 1-aminocyclopentane carbonitrile of formula II which reacts with aqueous hydrochloric acid to give aminocyclopentane carboxylic acid hydrochloride salt of formula XIV which on further reaction with valeroyl chloride, sodium hydroxide, toluene, tetrabutyl ammonium bromide and water (or by using valeroyl chloride and pyridine) to get 1-valeramido cyclo pentane carboxylic acid of formula XV. Compound XVcouples with 4'-aminomethyl biphenyl derivative to give an intermediate XIII which undergoes azidation to give Irbesartan as in the scheme VII.

CA2050769 describes the process which comprises the reaction of formula XVI with pentanoyl chloride to give formula XVII which is reduced in presence of solvent to give formula XVIII. Compound XVIII undergoes coupling with 4-aminomethyl-2'-cyanobiphenyl followed by recrystallization giving compound XIX. Compound of formula XIX reacts with PTSA monohydrate and toluene to give compound VI which undergoes azidation in presence of solvent such as o-xylene and is recrystallised from isopropyl alcohol to give Irbesartan of formula I as in scheme VIII.

US2005021535 describes the detrilyation process of trityl Irbesartan of formula VII which on reaction with solvent and under anhydrous conditions gives methyltriphenylmethyl ether of formula XX which is further evaporated, washed with ice -cold methanol, concentrated, cooled for the removal of ether, again evaporated, crystallized from isopropanol/ethanol; washed with hexane to give Irbesartan as in scheme IX given below.


US2006/0128967 provides a one pot method for the synthesis of trityl Irbesartan. It involves the multiphase system as described in five paths for the preparation of trityl Irbesartan of formula VII. i) 2'-(l-trityl-lH-tetrazol-5-yl)-4'-ylmethylamine of formula XXI is reacted with ethyl valerimidate methanesulfonic acid salt in dry toluene to give intermediate of formula XXII which undergoes coupling with 1-amino cyclopentane carboxylicacid ethyl ester to give trityl Irbesartan . ii) N- Pentanoylaminocyclopentanecarboxylic acidamide of formula Va couples with formula XXIII to give trityl Irbesartan. iii) 5-(4'-methyl valeramide-bi-phenyl-2-yl)-l-trityl-lH-tetrazole of formula XXIV couples with 1 -amino cyclopentane carboxylic acid ethylester to give trityl Irbesartan. iv) Formula XXIII couples with formula XXI to give trityl Irbesartan . v) N-valerimidate-1-aminocyclopentane carboxylic acid ethyl ester of formula XX imdergoes coupling with formula XXI to give trityl Irbesartan . Trityl Irbesartan finally undergoes detritylation in presence of acetone, aqueous 3N hydrochloric acid, potassium hydroxide in water, ethyl acetate to give Irbesartan as in scheme X.


US2005/0176794 describes the novel process for the preparation of Irbesartan by two phase system (first and second liquid phase). 2-butyl-l,3-diazaspiro[4.4]non-l-ene-4-one couples with 5-(4'-broniomethylbiphenyl-2-yl)-l-trityl-lH-tetrazole in the presence of first solvent like benzene, toluene, m-xylene, o-xylenes, tetralins; base such as potassium hydroxide, sodium hydroxide,lithium hydroxide and water acting as the second solvent, tetrabutyl ammonium hydrogen sulphate acting as the phase transfer catalyst along with acetone and hydrochloric acid to give Irbesartan as in scheme XI.

WO2006046043 describes the one pot synthesis of Irbesartan where 2-n-butyl-4-cyclopentane-2-imidazolin-5-one or its hydrochloride salt couples with 5-(4'- bromomethyl-biphenyl-2-yl)-l-triphenylmethyl-lH-tetrazole to give trityl Irbesartan. The ditritylation process is done by the reaction of trityl Irbesartan in presence of mineral acid to give Irbesartan hydrochloride which on purification gives Formula I or gives the free base Form A or Form B of Irbesartan as in Scheme XII.


WO2007115990 describes the process which comprises the reaction of trityl Irbesartan with water and water miscible organic solvent along with hydrohalic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid to give Irbesartan hydrohalide salt which is recrystallised from solvent such as acetone, tetrahydrofuran, 2-methyl-tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethyl acetamide, methanol, ethanol, propanol, 2-propanol and basified from base such as hydrogen carbonates, hydroxides and alkoxydes to give Irbesartan as in Scheme XIII.

WO2006125592 comprises the coupling of 2-butyl-l,3-diazaspiro[4.4]non-l-en-4-one and 4-bromomethylphenyl boronic acid of formula XXV in presence of base and solvent to give an intermediate 4-[(2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yl)methyl]phenylboronic acid of formula XXVI which undergoes Suzuki coupling with 5-(2-bromophenyl)-l-(triphenylmethyl)-lH-tetrazole in presence of solvent as used in first step along with base and catalyst to give trityl Irbesartan.The compound of formula XXV couples with 2'-propyl-l,4'-dimethyl-2,6'-bi(lH-benzo [d]imidazole)of formula XXVII to give 4'-[(1,4'-dimethyl-2'-propyl-[2,6'-bi-lH-benzimidazol]-1’- yl)methyl]phenylboronic acid of formula XXVIII and finally couples with 2-broniobenzoic acid to give compound XXDC as in Scheme XV.

WO2005051943 describes the process which comprises reaction of 2-n-butyl-l,3-diazaspiro[4.4]non-l-ene-4-one with 4'-bromomethyl[l,1’-biphenyl]-2-carbonitrile in presence of solvent such as - methanol, ethanol, isopropanol, n-propanol, tetrahydrofuran, acetonitrile, 1,4- dioxane, dimethylformamide, dimethylsulphoxide and base like sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, potassium methoxide, potassium t-butoxide to give an cyano intermediate of formula V. The compound of formula V is cyclized to a tetrazole group by reacting with phase transfer catalyst which is cyclized to a tetrazole group in presence of solvent to give Irbesartan of formula I which may be protected by treating with conventional protecting agents and simultaneously deprotected in presence of deprotecting agents and suitableorganic solvents as given in Scheme XV.

US5399578 describes the process which comprises the reaction of compound of formula XXX with 4'-aminomethyl[1,1 '-biphenyl] 2-carbonitrile in presence of base and dimethylformamide to give an intermediate of formula XXXI which undergoes deprotection to give an intermediate of formula XXXII. The compound XXXII reacts with valeroyl chloride to give compound XXXIII which is acidified to give compound of formula VI which can either be be converted to Irbesartan via trityl Irbesartan by cyclization, protection and deprotection as in Scheme XVI.

WO2007122508 setforths the path a) where 4'-aminomethyl [1,1 '-biphenyl] 2-carbonitrile is converted to its acetamide derivative which couples with N-pentanoyl aminocyclopentane carboxylic acid to give an intermediate 4-[(a-N-pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl of formulas XXXIII which on cyclization and simultaneous reduction in presence of solvent gives compound VI which is azilated to give Irbesartan. Similarly other paths involve the intermediate XXXIII which undergoes azidation in presence of solvent to give Irbesartan as give in Scheme XVII.

WO2006089927 explains the process comprising three paths for the preparation of Irbesartan intermediate. The path (a) involves reaction of 1-tert-butoxy carbonyl amine-cyclopentano carboxylic acid with 4-iodobenzyl bromide to give an diamide intermediate of formula XXXV which on reduction and cyclization gives 2-butyl-3-(4'-iodobenzyl)-l,3-diazaspiro[4.4] non-l-en-4-one of formula VIb. The path (b) elucidates the coupling of 1-pentanoylaminecyclopentano carboxamide of formula XVa with 4-iodobenzylbromide to give compound VI b.

Path (c) involves the conversion of 1-pentanoylamine cyclopentanocarboxylic acid to give diamide intermediate of formula XXXVII which undergoes cyclization to give intermediate VIb. Finally 2-butyl-3-(4'-iodobenzyl)-l,3-diazaspiro[4.4] non-l-en-4-one couples with 2-(lH-tetrazol-5-yl) phenylboronic acid of formula in presence of solvent, base, catalyst and recrystallised to give Irbesartan.

WO2007/017469 describes the process for the preparation of intermediate 2*-(lH-tetrazol-5-yl) biphenyl-4-yl)methanamine hydrochloride used for the preparation of Irbesartan . a) Compound Xa couples with 4-(bromophenyl) methanamine hydrochloride to give (2'-(lH-tertazol-5-yl)biphenyl-4-yl)methanamine hydrochloride of formula XXXVIIL b) 5-phenyl-lH-tetrazole couples with 4-(bromophenyl) methanamine hydrochloride in presence of 1,2-dimethoxyethane to give intermediate XXXVIII. c) N-(2'-(l-trityl-lH-tetrazol-5-yl)biphenyl-4-yl)methyl hexamethylenetetramine bromide is prepared by coupling of 5-(4'-(bromomethyl) biphenyl-2-yl)-l-trityl-lH-tetrazole and hexamethylene tetramine The compound V and compound XXXVIII couples to give Irbesartan of formula I.

WO2008027385 elucidates that 5-phenyl-lH-tetrazole of formula undergoing basification in presence of base, water using phase transfer catalyst in an organic solvent and trityl compound to give 5-phenyl-l-trityl-lH- tetrazole of formula which further reacts with borate and base to give 2-[5-(l-trityl-lH-tetrazol)phenylboronic acid] of formula X. Coupling of the compound X and 2-butyl -3(4'-bromobenzyl)-l,3-diazaspiro[4,4]non-l-ene-4-one in presence of catalyst and solvent to give trityl Irbesartan of formula VII which on further acidification in presence of solvent gives Irbesartan as given in Scheme XX.

The crude Irbesartan is crystallized in a mixture of water and water miscible solvent such as ethanol, isopropanol, acetonitrile , acetone , dioxide, tetrahydrofiiran, methyl t-butyl ether, solvent such as formic acid, acetic acid and pyromaniac acid containing water (5% to 40 %) to get Irbesartan polymorph Form A.

The Irbesartan polymorph form A can be converted to Irbesartan polymorph form B by recrystallization and vice-versa.

SUMMARY OF THE INVENTION

Accordingly the principal aspect of the invention is to to provide an improved process for preparation of 2-butyl-3-[[2’(1H -tetrazol-5-yl)[l,1’iphenyl]-4-yl]methyl]-l,3-diazaspiro [4.4] non -l-en-4-one polymorph form A of formula I which is cost effective and commercially viable

• coupling of 2-n-butyl-4- cyclopentane-2-imidazolin-5-one hydrochloride of formula 11 with 4'-(bromomethyl)[1,1’-enyl]-2-carbonitrile of formula III to give 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yl]methyl][l,1’iphenyl]-2-carbonitrile of formula IV;

• conversion of 4'-[[2-butyl-4-oxo-l,3-dia2aspiro[4.4]non-l-en-3-Yl]methyl][l,1’iphenyl]-2-carbonitrile to 2-butyl-3-[[2'-(1H -tetrazol-5-yl)[l,1’iphenyl]-4-yl]methyl]-l,3-diazaspiro [4.4]non-l-en-4-one of formula I; and

• purification of 2-butyl-3-[[2'-(1H -tetrazol-5-yl)[l,1’iphenyl]-4-yl]methyl]-l,3-
diazaspiro [4.4]non-l-en-4-one to Irbesartan Form A.

DETAILED DESCRIPTION OF THE INVENTION

The detail description of synthesis of Irbesartan Form A which is cost effective and commercial viable as given in Scheme which comprises :

• coupling of 2-n-butyl-4- cyclopentane-2-imidazolin-5-one hydrochloride of formula II with 4'-(promomethyl)[ 1,1 -biphenyl]-2-carbonitrile of formula III to give 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-1 -en-3-yl]methyl] [1,1’biphenyl]-2-carbonitrile of formula IV;

• conversion of 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yl]methyl][l,1’phenyl]-2-carbonitrile to 2-butyl-3-[[2'-(1H -tetrazol-5-yl[ 1,1 '-biphenyl]-4-yl]methyl]-l ,3-diazaspiro [4.4]non-l-en-4-one of formula I; and

• purification of 2-butyl-3-[[2'-(lH-tetrazol-5-yl)[l,1’biphenyl]-4-yl]methyl]-l,3-diazaspiro[4.4] non-l-en-4-one to Irbesartan Form A.


In an embodiment of the invention, 2-n-butyI-4- spirocyclopentane-2-imida2olin-5-one hydrochloride of formula 11 is reacted with 4'-(bromomethyl) [1,1-biphenyl]-2-carbonitrile of formula III in presence of a base such as sodium hydride, potassium borohydride and aprotic solvent such as dimethylformamide to give 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yI] ethyl] [l,1’-biphenyl]-2-carbonitrile of formula IV.
In another embodiment of the invention, 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yljmethyl] [l,1’-biphenyl]-2-carbonitrile of formula IV is reacted with triethylamine hydrochloride and an azylating agent such as sodium azide, potassium azide and like, preferably sodium azide in presence of phase transfer catalyst selected from the group consisting of crown ethers, quaternary ammonium slats, polyethylene glycols, preferably polyethylene glycol and solvent such as substituted and unsubstantiated aromatic hydrocarbon such as xylene. It is further acidified with acid such as hydrochloric acid, sulphuric acid preferably with hydrochloric acid. The pH of the reaction mixture was increased by addition of base such as potassium hydroxide to give crude 2-butyl-3-[[2'-(1H -tetrazol-5-yl)[1,1’-biphenyl]-4-yl] methyl] -l,3-diazaspiro[4.4]non-l-en-4-one (Irbesartan) of formula I.

In yet another embodiment of the invention, Irbesartan is recrystallised by alcoholic solvent such as C1-C4 alcohol such as methanol, ethanol, propanol and the like, preferably methanol to give the polymorphic form A of Irbesartan.

The present invention can be illustrated by the following examples, which should not be construed to limit the scope of invention in anyway.

Example 1
Preparation of 4’-[[2-butyl-4-oxo-1,3-diarzaspiro[4.4]non-l-en-3-yl methyl] [1,1’-2-biyhenyl-2-carhonitrile

4'-Bromomethyl-biphenyl-2-carbonitrile(59.0gms) was reacted with NaH in DMF under nitrogen atmosphere. The reaction mixture was cooled to 10-15°C with the simultaneous addition of 2n-butyl-4-spu'ocyclopentane-2-imidazolin-5-one hydrochloride (50.0gms) and stirred for 15mins. 4’-(Bromomethyl) [1,1-biphenyl]-2-carbonitrile was added completely at the duration of l.0 hr at a temperature 25-30°C. Acetic acid (0.01 L) was added to the reaction mixture and dumped to DM-water (0.700 L) and ice and with continuous stirring toluene (0,400 L) was added. The reaction mixture was allowed to settle for 30 min. Layers were separated with the addition of toluene to the aqueous layer. The reaction mixture was stirred and settled for 30 minutes. The organic layer was charged with sodium sulphite, filtered, washed with toluene, distilled under vacuum below 65°C. Hexane(0.30 L) was added to the reaction mixture, stirred, filtered and dried for 8.0 hrs to give 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yl] methyl] [l,1’-biphenyl]-2-carbonitrile(Yield: 84.31%, HPLC Purity: 95.45%)

Example 2

Preparation of Crude2-butyl-3-[[2’-(lH-tetrazol-5-yl)[11’-biphenyl1-4-yl]methyl]-l,3'diazaspiro [4,4] non-l-en-4'One polymorphic form A

4'-[[2-Butyl-4-oxo-l,3-diazaspiro [4.4] non -l-en-3-yl] methyl] [l,1’-biphenyl]-2-carbonitrile (30.0gms) was added to a stirred mixture of "NaN3 (30.7gms), triethylamine hydrochloride (53.5gms) and xylene (0.300 L). The reaction mixture was refluxed upto 110-115°C with the addition of polyethylene glycol-400 (0.036 L) and the temperature was maintained for 32 hrs. Mixture was cooled to 0-5°C, methanol (0.150 L) was added and pH was adjusted to 3.5 with 1:1 hydrochloric acid solution. The reaction mass was stirred for 15 minutes and pH was again adjusted to 11.0 with 10%o KOH solution. The temperature was maintained at 25-30°C, layers were separated and aqueous layer was washed with toluene (0,450 L) thrice. Separation of layers was done, ethyl acetate was added to the aqueous layer, pH was adjusted to 4 - 4.5 with 1:1 HCl solution. The reaction mixture was stirred for vomited(12hrs), fathered, washed with ethyl acetate twice, dried for 8.0 hrs at 50-55°C under vacuum to give crude Irbesartan (Yield:75.94%, HPLC Purity: 98.97%).

Example 3

Purification of Crude 2-butyl-3-[[2’-1H-tetrazol-5-yl)[1,1’biphenyl]-4'y1]methyl]-1,3-diazaspiro[4,4] non-1'en-4-one polymorphic form A

Crude Irbesartan (23.0gms) was charged with methanol (0.517 L) and refluxed for 1.0 hrs to get a clear solution. The solution was filtered, washed with methanol, cooled to 0-5°C, stirred for 1.0 hrs and again filtered, washed with methanol. Refluxed, cooled from 25-30°C to 0-5°C and the temperature was maintained for 1 hr, filtered, washed with methanol an dried for 8.0 hrs at 50-55°C under vacuum to get Irbesartan(Yield: 71.7%, HPLC Purity : 99.92%)

We Claim:

1. A process for preparation of Irbesartan of Formula I, which comprises:

a) condensation of ng a 2-n-butyl-4- cyclopentane-2-imidazolin-5-one hydrochloride of formula ( II ) with 4'-(bromomethyl)[1,1-biphenyl]-2-carbonitrile of formula (III) to obtain 4'-[[2-butyl-4-oxo-l,3-diazaspiro[4.4]non-l-en-3-yl]methyl][l,1’-biphenyl]-2-carbonitrile of formula IV;

b) converting compound of formula (IV) in presence of sodium azide and triethylamine hydrochloride to Irbesartan of formula I; and

c) optional purification of the obtained Irbesartan of formula I to obtain pure Irbesartan form A.

2. The process according to claim l, wherein the compound of formula (IV) in step (b) is converted to Irbesartan in presence of a phase transfer catalyst.

3. The process according to claim 2, where in phase transfer catalyst is selected from the group consisting of crown ethers, quaternary ammonium slats, polyethylene glycols.

4. The process according to claim 2, where in phase transfer catalyst is polyethylene glycols.

5. The process according to claim 1, where in the irbesartan of Formula I has a purity greater than about 99.97%.