The present invention relates to improved processes for preparing intermediates of valsartan or its salts.
Valsartan is chemically described as (S)-N-(1-carboxy-2-methylprop-1-yl)N-pentanoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine of Formula I.
(Formula Removed)

Valsartan is an angiotensin II antagonist acting on the AT1 receptor subtype. It is useful for the prophylaxis and treatment of diseases or conditions, which may be inhibited by blocking the ATi receptor such as high blood pressure and cardiac insufficiency.
Processes for the synthesis of valsartan and its intermediates are provided several prior art references including US Patent No. 5,399,578, US Patent Application Publication No. 2006/0069268, US Patent Application Publication No. 2006/010043, US Patent No. 6,271,375 and Org. Process Res. Dev., 2007, 11(5) 892-898.
The compounds of Formula II and Formula VI are important intermediates for the preparation of valsartan.

(Formula Removed)

US Patent No. 5,399,578 provides a process for the preparation of the compound of Formula II by reacting a compound of Formula III
(Formula Removed)

with tosylate salt of a compound of Formula IV
(Formula Removed)

Org. Process Res. Dev., 2007, 11(5) 892-898 provides a process for the preparation of the compounds of Formula II and Formula VI without using any alkylamine. According to said process, the compound of Formula II is prepared by reacting the compound of Formula III with the free base form of the compound of Formula IV in xylene at 60°C for 2 hours. The compound of Formula II is isolated as a hydrochloride salt from xylene solution by the addition of aqueous hydrochloric acid at 72°C under vigorous stirring for 2 hours and by removing the water continuously by Dean-Stark distillation. The hydrochloride salt of the compound of Formula II is further converted into its free base form by stirring at 50°C for 30 minutes in the presence of sodium hydroxide, water and xylene. The compound of Formula II obtained as a free base is reacted with the compound of Formula V in xylene in the presence of aqueous sodium hydroxide at 40°C for 2 hours to obtain the compound of Formula VI. The compound of Formula VI is isolated by treating with ammonia solution, layer separation and distillation.
However, the process provided in Org. Process Res. Dev., 2007, 11(5) 892-898 invloves use of high-boiling solvents such as xylene or toluene and thus, requires high temperature conditions. Carrying out these reactions at higher temperature conditions is likely to result into degradation of the products and requires employing further purification steps, which are lengthy and uneconomical. The process provided in Org. Process Res. Dev., 2007, 11(5) 892-898 also requires converting the salt forms of the compounds for Formula IV and Formula II into their free base forms prior to further reactions. The processes provided in US Patent No. 5,399,578 and US Patent Application Publication No. 2006/0281801 involve the use of diisopropylethylamine at least in one of the steps, which is reported to lead to the formation of impurities, and these processes also require heating at higher temperature conditions for long time.
The present inventors have found that the problems associated with the prior art processes can be avoided by using a phase transfer catalyst for preparing the compounds of Formula II
in dimethylformamide in the presence of diisopropylethylamine. The reaction is carried out by stirring the reaction mixture at 80°C for 1 hour.
The compound of Formula II is further reacted with a compound of Formula V
(Formula Removed)

in methylene chloride in the presence of diisopropylethylamine to obtain the compound of Formula VI. The reaction is carried out by stirring the reaction mixture at room temperature for 20 to 25 hours. The compound of Formula VI is finally reacted with tributyltin azide and deprotected to obtain valsartan.
US Patent Application Publication No. 2006/0281801 provides a process for the preparation of the compound of Formula II by reacting the compound of Formula III and tosylate salt of the compound of Formula IV in a solvent system containing toluene or xylene and water. The reaction is carried out by heating the reaction mixture to 50° to 55°C for 25 hours in the presence of potassium carbonate and tetrabutylammonium bromide followed by acidification with hydrochloric acid to obtain the compound of Formula II as a hydrochloride salt with 97% purity. The hydrochloride salt of the compound of Formula II is converted to its free base form by treating with aqueous sodium bicarbonate in toluene. The compound of Formula II obtained as a free base is reacted with the compound of Formula V in toluene in the presence of diisopropylethylamine at 20°C for 30 minutes to obtain the compound of Formula VI. The compound of Formula VI is isolated with 96% purity after acid-base treatments and layer separation.
Org. Process Res. Dev., 2007, 11(5) 892-898 says that the use of diisopropylethylamine in the preparation of the compounds of Formula II and Formula VI leads to the formation of byproducts including (S)-3-methyl-2-pentanoylamino-butyric acid benzyl ester of Formula VII and pentanoic acid anhydride of Formula VIII in 5 to 8 mol % each.
and Formula VI. The present processes for the preparation of compounds of Formula II and Formula VI also avoids the use of diisopropylethylamine. Further, higher temperature conditions are not needed for the present processes. The compounds for Formula IV and Formula II can be employed in the present processes either in free base form or in their salt forms without any necessity of liberating them as free bases. Thus, the present invention substantially minimizes the process steps, the formation of byproducts, avoids the necessity of employing any additional purification steps and helps to obtain valsartan with higher purity. The present process is also suitable for preparing valsartan at industrial scale.
A first aspect of the present invention provides a process for preparing the compound of Formula II having purity of about 98.0% or above, or its salts,

(Formula Removed)
comprising reacting the compound of Formula III

(Formula Removed)
with the compound of Formula IV or its salt
(Formula Removed)
in the presence of a phase transfer catalyst.
The compound of Formula III may be prepared by the methods known in the prior art, for example, Org. Process Res. Dei/., 2007, 11(5) 892-898. The compound of Formula IV may be used as a free base or in the form of its salt, for example, the tosylate salt.
The reaction of the compound of Formula III and the compound of Formula IV or its salt may be carried out in the presence of a solvent system comprising of water and one or more water immiscible organic solvents. Examples of water immiscible organic solvents include halogenated hydrocarbons, esters, ethers and mixtures thereof. Examples of halogenated hydrocarbons include dichloromethane, ethylene dichloride, chloroform and mixtures thereof. Examples of esters include ethylacetate, isopropylacetate and mixtures thereof. Examples of ethers include diethyl ether, diisopropylether and mixtures thereof. The solvent system is preferably a mixture of water and a halogenated hydrocarbon, for example, dichloromethane.
The reaction may be carried out in the presence of a base. The base may be an inorganic base. Examples of inorganic base include alkali metal carbonates, bicarbonates, hydroxides and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate, sodium carbonate and potassium carbonate. Examples of alkali metal bicarbonate include sodium bicarbonate and potassium bicarbonate. Examples of alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Preferably potassium carbonate is used as the base.
The phase transfer catalyst employed in the reaction of the compound of Formula III with the
compound of Formula IV may be selected from the group consisting of tetrabutylammonium
bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride,
tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen
sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride,
tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide, and ethyltriphenylphosphonium iodide. Preferably tetrabutylammonium bromide may be used as the phase transfer catalyst.
The reaction may be carried out at a temperature range less than about 40°C, for example, at about -20° to about 35°C. Preferably the reaction may be carried out at about 20° to about 35°C. The reaction may be facilitated by stirring the reaction mixture for up to about 30 hours, for example, about 15 hours to about 25 hours. The compound of Formula II is obtained with a purity of about 98.0% or above, preferably with a purity of about 99.0% or above, more preferably with a purity of about 99.5% or above.
The compound of Formula II may be isolated as a free base or as a salt from the reaction mixture. The compound of Formula II may be isolated, for example, as an acid addition salt by treating the reaction mixture with an acid, for example, hydrochloric acid. The isolation of the compound of Formula II or its salts may be performed by the methods including layer separation, concentration, precipitation, filtration, decantation, distillation or a combination thereof.
A second aspect of the present invention provides a process for preparing the compound of Formula VI
(Formula Removed)
comprising reacting the compound of Formula II or its salt

(Formula Removed)
with the compound of Formula V

(Formula Removed)
in the presence of a phase transfer catalyst.
The compound of Formula II may be prepared according to the previous aspect of the present invention or by the methods known in the prior art, for example Org. Process Res. Dev., 2007, 11(5) 892-898. The compound of Formula II may be used as a free base or in the form of its salt, for example, the tosylate salt.
The reaction of the compound of Formula II or its salt with the compound of Formula V may be carried out in the presence of a solvent system comprising of water and one or more water immiscible organic solvents. Examples of water immiscible organic solvents include halogenated hydrocarbons, esters, ethers and mixtures thereof. Examples of halogenated hydrocarbons include dichloromethane, ethylene dichloride, chloroform and mixtures thereof. Examples of esters include ethylacetate, isopropylacetate and mixtures thereof. Examples of ethers include diethyl ether, diisopropylether and mixtures thereof. The solvent system is preferably a mixture of water and a halogenated hydrocarbon, for example, dichloromethane.

The reaction may be carried out in the presence of a base. The base may be an inorganic base. Examples of inorganic base include alkali metal carbonates, bicarbonates, hydroxides and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate, sodium carbonate and potassium carbonate. Examples of alkali metal bicarbonate include sodium bicarbonate and potassium bicarbonate. Examples of alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Preferably potassium carbonate is used as the base.
The phase transfer catalyst employed in the reaction of the compound of Formula II with the
compound of Formula V may be selected from the group consisting of tetrabutylammonium
bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride,
tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen
sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride,
tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide, and ethyltriphenylphosphonium iodide. Preferably tetrabutylammonium bromide may be used as the phase transfer catalyst.
The reaction may be carried out at a temperature range less than about 40°C, for example, at about -20° to about 35°C. Preferably the reaction may be carried out at about -10° to about 5°C. The reaction may be facilitated by stirring the reaction mixture for up to about 30 hours, for example, about 30 minutes to about 5 hours.
The compound of Formula VI may be isolated from the reaction mixture or used in the subsequent steps of preparing valsartan without isolation. The compound of Formula II may be optionally isolated by the methods including layer separation, concentration, precipitation, filtration, decantation, distillation or a combination thereof.
A third aspect of the present invention provides a process for preparing the compound of Formula VI
(Formula Removed)

comprising the steps of
a) reacting the compound of Formula III
(Formula Removed)

with the compound of Formula IV or its salt
(Formula Removed)

in the presence of a phase transfer catalyst to obtain the compound of Formula II or its salt, and
(Formula Removed)

b) reacting the compound of Formula II or its salt with the compound of Formula V

(Formula Removed)
in the presence of a phase transfer catalyst to obtain the compound of Formula VI.
The compound of Formula III may be prepared by the methods known in the prior art, for example Org. Process Res. Dev., 2007, 11(5) 892-898. The compound of Formula IV may be used as a free base or in the form of its salt, for example, the tosylate salt.
The reaction of the compound of Formula III and the compound of Formula IV or its salt may be carried out in the presence of a solvent system comprising of water and one or more water immiscible organic solvents. Examples of water immiscible organic solvents include halogenated hydrocarbons, esters, ethers and mixtures thereof. Examples of halogenated hydrocarbons include dichloromethane, ethylene dichloride, chloroform and mixtures thereof. Examples of esters include ethylacetate, isopropylacetate and mixtures thereof. Examples of ethers include diethyl ether, diisopropylether and mixtures thereof. The solvent system is preferably a mixture of water and a halogenated hydrocarbon, for example, dichloromethane.
The reaction may be carried out in the presence of a base. The base may be an inorganic base. Examples of inorganic base include alkali metal carbonates, bicarbonates, hydroxides

and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate, sodium carbonate and potassium carbonate. Examples of alkali metal bicarbonate include sodium bicarbonate and potassium bicarbonate. Examples of alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Preferably potassium carbonate is used as the base.
The phase transfer catalyst employed in the reaction of the compound of Formula III with the
compound of Formula IV may be selected from the group consisting of tetrabutylammonium
bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride,
tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen
sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride,
tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide, and ethyltriphenylphosphonium iodide. Preferably tetrabutylammonium bromide may be used as the phase transfer catalyst.
The reaction may be carried out at a temperature range less than about 40°C, for example, at about -20° to about 35°C. Preferably the reaction may be carried out at about 20° to about 35°C. The reaction may be facilitated by stirring the reaction mixture for up to about 30 hours, for example, about 15 hours to about 25 hours. The compound of Formula II is obtained with a purity of about 98.0% or above, preferably with a purity of about 99.0% or above, more preferably with a purity of about 99.5% or above.
The compound of Formula II may be isolated as a free base or as a salt from the reaction mixture. The compound of Formula II may be isolated, for example, as an acid addition salt by treating the reaction mixture with an acid, for example, hydrochloric acid. The isolation of the compound of Formula II or its salts may be performed by the methods including layer separation, concentration, precipitation, filtration, decantation, distillation or a combination thereof.
The reaction of the compound of Formula II or its salt is reacted with the compound of Formula V. The reaction may be carried out in the presence of a solvent system comprising of water and one or more water immiscible organic solvents. Examples of water immiscible organic solvents include halogenated hydrocarbons, esters, ethers and mixtures thereof. Examples of halogenated hydrocarbons include dichloromethane, ethylene dichloride, chloroform and mixtures thereof. Examples of esters include ethylacetate, isopropylacetate and mixtures

thereof. Examples of ethers include diethyl ether, diisopropylether and mixtures thereof. The solvent system is preferably a mixture of water and a halogenated hydrocarbon, for example, dichloromethane.
The reaction may be carried out in the presence of a base. The base may be an inorganic base. Examples of inorganic base include alkali metal carbonates, bicarbonates, hydroxides and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate, sodium carbonate and potassium carbonate. Examples of alkali metal bicarbonate include sodium bicarbonate and potassium bicarbonate. Examples of alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Preferably potassium carbonate is used as the base.
The phase transfer catalyst employed in the reaction of the compound of Formula II with the
compound of Formula V may be selected from the group consisting of tetrabutylammonium
bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride,
tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen
sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride,
tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide, and ethyltriphenylphosphonium iodide. Preferably tetrabutylammonium bromide may be used as the phase transfer catalyst.
The reaction may be carried out at a temperature range less than about 40°C, for example, at about -20° to about 35°C. Preferably the reaction may be carried out at about -10° to about 5°C. The reaction may be facilitated by stirring the reaction mixture for up to about 30 hours, for example, about 30 minutes to about 5 hours.
The compound of Formula VI may be isolated from the reaction mixture or used in the subsequent steps of preparing valsartan without isolation. The compound of Formula II may be optionally isolated by the methods including layer separation, concentration, precipitation, filtration, decantation, distillation or a combination thereof.
The compound of Formula VI so obtained is further converted into valsartan or its salts by the methods known in the prior art, for example, PCT Publication No. WO 05/049588, PCT Publication No. WO 05/049587, US Patent Application Publication No. 2006/0281801 and US Patent No. 5,399,578. The conversion of the compound of Formula VI into valsartan or its salts

may be carried out by reacting the compound of Formula VI with tributyltin halide and sodium azide to obtain benzyl protected valsartan, which is deprotected to obtain valsartan or its salts. The reaction of the compound of Formula VI with tributyltin halide and sodium azide may be carried out in the presence of an organic solvent, for example, toluene or xylene. The reaction may be carried out at reflux temperature. The benzyl protected valsartan may be deprotected by hydrogenation with palladium-carbon in the presence of an organic solvent, for example, ethyl acetate, to obtain valsartan. The valsartan may be isolated as a salt, for example, as a barium salt by treating with barium hydroxide. The salt of valsartan may be further converted into valsartan by treating with an acid, for example, hydrochloric acid. The valsartan or its salt so obtained has a purity of about 99.0% or above, preferably about 99.9%.
In the following section embodiments are described by way of examples to illustrate the process of invention. However, these are not intended in any way to limit the scope of the present invention. Several variants of these examples would be evident to persons ordinarily skilled in the art.
EXAMPLES
EXAMPLE 1
PREPARATION OF (S)-N-[(2'-CYANOBIPHENYL4-YL)METHYL]-(L)-VALINE BENZYL
ESTER HYDROCHLORIDE :
The mixture of potassium carbonate (152.2 g) and de-mineralised water (300 ml) was stirred for 10-15 minutes to dissolve the solid. The temperature of the mixture was maintained at 30-35°C and dichloromethane (300 ml) was added. It was then added L-valine benzyl ester tosylate (153.3 g), tetrabutyl ammonium bromide (10.0 g) and 4-bromomethyl-2'-cyanobiphenyl (100 g). The reaction mixture was stirred for 20-24 hours at 30-35 °C. After completion of the reaction DM water (400 ml) was added and the mixture was stirred for 5 minutes. The two phases were separated and aqueous layer was extracted with dichloromethane (200 ml). The combined organic layer was washed with DM water (300 ml) and was concentrated at 40-45°C. Ethyl acetate (600 ml) was then added to the residue and was stirred for 5-10 minutes to dissolve the residue. The reaction mixture was cooled to 0-5°C and concentrated hydrochloric acid (50 ml) was added. The mixture was stirred for one hour. Precipitated solid was filtered,

washed with ethyl acetate and dried to give 140 g of (S)-N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride having a purity of 99.6% as measured by HPLC area percent.
EXAMPLE 2
PREPARATION OF (S)-N-[(2,-CYANOBIPHENYL-4-YL) METHYL]-N-VALEROYL-(L)-
VALINE BENZYL ESTER:
The mixture of potassium carbonate (95.3 g) and DM water (100 ml) was stirred for 10-15 minutes to dissolve the solid. The temperature of the mixture was maintained at 25-30°C and dichloromethane (300 ml) was added. It was then added (S)-N-[(2'-cyanobiphenyl4-yl)methyl]-(L)-valine benzyl ester hydrochloride (100 g) and tetrabutyl ammonium bromide (10.0 g). The reaction mixture was cooled to -10 to -8°C and valeryl chloride (36.1 g) was added at -10 to -5°C. The reaction mixture was stirred for 60-90 minutes at 0-5 °C. After completion of the reaction the temperature was raised to 25-30°C. DM water (200 ml) was added and the mixture was stirred for one hour at 25-30°C. The two phases were separated and organic layer was washed with DM water (200 ml). The organic layer was concentrated at 40-45°C. The residual liquid was used as such for next step.
EXAMPLE 3
PREPARATION OF (S)-N-(1 -BENZYLOXYCARBONYL-2-METHYL-PROP-1 -YL)-N-
PENTANOYL-N-[2'(1H -TETRAZOL-5-YL)BIPHENYL-4-YL-METHYL] AMINE:
A mixture of the N-[(2'-cyanobiphenyl -4-yl) methyl]-N- pentanoyi - (L)-valine benzyl ester as obtained above, tributyltin chloride (150 g), sodium azide (30 g) and tetra butyl ammonium bromide(10 g) in toluene(200ml) was refluxed for 30 hours. After completion of the reaction it was cooled and stirred with solution of Toluene (200ml), DM water (400ml) and acetic acid (60ml) for 1 hour. Organic layer was separated, concentrated and dissolved in 1, 4-dioxane (500ml). It was then cooled to 10-15°C and stirred with the solution of sodium hydroxide (27.6 g in 690ml water) at 0-5°C for 1 hour. Aqueous layer was extracted twice with diisopropyl ether, acidified and extracted with ethylacetate. Ethyl acetate layer was concentrated at reduced pressure to obtain title compound as oil.
EXAMPLE 4
PREPARATION OF (S)-N-(1 -CARBOXY-2-METHYL-PROP-1 -YL)-N-PENTANOYL-N-[2'(1 H-
TETRAZOL-5-YL)BIPHENYL-4-YL-METHYL]AMINE BARIUM SALT (VALSARTAN
BARIUM):

A solution of (S)-N-(1-benzyloxycarbonyl-2-methyl-prop-1-yl)-N-pentanoyl-N-[2'(1H -tetrazol-5-yl)biphenyl-4-yl-methyl] amine obtained above in ethyl acetate was hydrogenated with palladium carbon (10g) at 50-55°C for 8 hours. After completion of the reaction, it was filtered, concentrated and dissolved in acetone (800ml). This solution was treated with aqueous barium hydroxide solution (72.6 g) at 15-35°C.lt was then stirred at 0-5°C for 5 hours. Solid obtained was filtered, washed with acetone and dried to obtain title salt as white crystalline solid. Yield: 105 g HPLC Purity: 99.9 %
EXAMPLE 5
PREPARATION OF (S)-N-(1-CARBOXY-2-METHYL-PROP-1-YL)-N-PENTANOYL-N-[2'(1H -TETRAZOL-5-YL)BIPHENYL-4-YL-METHYL] AMINE (VALSARTAN)
Slurry of valsartan barium (90g) in ethyl acetate (900ml) and water (360ml) was treated with hydrochloric acid to adjust pH to about 2-2.5. Organic layer was separated, washed with water thrice (270ml each) and concentrated at about 45 to 50°C under reduced pressure. The residue was dissolved in ethyl acetate (225ml) at 45-50°C, filtered hot and cooled to room temperature. Pentane (900ml) was then added slowly and stirred for 1 hour at room temperature. Solid obtained was filtered, washed with pentane (2x90ml) and dried under reduced pressure to obtain valsartan. Yield: 60 g Assay: 100.4% Chiral purity: 99.9% HPLC purity: 99.9%

WE CLAIM:
1. A process for preparing the compound of Formula II having purity of about 98.0% or above, or its salts,
(Formula Removed)

comprising reacting the compound of Formula III

(Formula Removed)

with the compound of Formula IV or its salt
(Formula Removed)

in the presence of a phase transfer catalyst.
2. A process as claimed in claim 1 wherein the reaction is carried out in the presence of a solvent system comprising of water and one or more water immiscible organic solvents.
3. A process as claimed in claim 2 wherein the water immiscible organic solvent is a halogenated hydrocarbon, ester, ether or mixtures thereof.
4. A process as claimed in claim 1 wherein the phase transfer catalyst is selected from the group consisting of tetrabutylammonium bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride, tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen sulfate, benzylthmethylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide and ethyltriphenylphosphonium iodide.
5. A process as claimed in claim 4 wherein the phase transfer catalyst is tetrabutylammonium bromide.
6. A process as claimed in claim 1 wherein of the process further comprises converting the compound of Formula II having purity of about 98.0% or above, or its salts, into valsartan or its salts.

7. A process for preparing the compound of Formula VI
(Formula Removed)
comprising reacting the compound of Formula II or its salt
(Formula Removed)

with the compound of Formula V
(Formula Removed)

in the presence of a phase transfer catalyst.
8. A process as claimed in claim 7 wherein the phase transfer catalyst is selected from the group consisting of tetrabutylammonium bromide, tetrapropylammonium bromide, tributylbenzylammonium chloride, tetraethylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium hydrogen sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium acetate, tetrabutylammonium iodide, ethyltriphenylphosphonium bromide and ethyltriphenylphosphonium iodide.
9. A process for preparing the compound of Formula VI
(Formula Removed)

comprising the steps of
a) reacting the compound of Formula III
(Formula Removed)

with the compound of Formula IV or its salt
I(Formula Removed)
in the presence of a phase transfer catalyst to obtain the compound of Formula II or its salt, and

(Formula Removed)
b) reacting the compound of Formula II or its salt with the compound of Formula V
(Formula Removed)
in the presence of a phase transfer catalyst to obtain the compound of Formula VI.
10. A process as claimed in any one of claims 7 and 9 wherein of the process further comprises converting the compound of Formula VI into valsartan or its salts.