This application claims priority to Indian patent application 1310/CHE/2010 filed on May 11, 2010, the contents of which are incorporated by reference in their entity.

FIELD OF THE INVENTION:

The present invention relates to an improved process for the preparation of Montelukast sodium.

BACKGROUD OF THE INVENTION:

Montelukast Sodium is chemically known as l-[[[(1R)-l-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl)]phenyl]-3 -[2-( 1 -hydroxy-1 -methylethyl)phenyl]propyl]thio] methyl cyclo propane acetic acid and has the following structural formula:

Montelukast sodium is a leukotriene anatagonist and inhibits the synthesis of leukotriene biosynthesis. It is useful as anti-asthamatic, anti-allergic, anti-inflammatory, cytoprotective agent and hence useful in the treatment of angina, cerebral spasm, glomerular nephritis, hepatic endotoxemia, uveitis and allograft rejection.

EP 0 480 717 discloses Montelukast sodium along with other related compounds and methods for their preparation. The reported method of synthesis proceeds through corresponding methyl ester namely, Methyl 2- [(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-hydroxypropyl] benzoate and involves coupling methyl l-(mercaptomethyl) cyclopropane acetate with a mesylate generated in-situ. The methyl ester is hydrolyzed to free acids and the latter converted directly to Montelukast sodium salt (Scheme-1). The process is not suitable for large scale production as it requires tedious chromatographic purification of methyl ester intermediate and/or the obtained final product is low in yield.

Scheme 1

Montelukast is a chiral molecule and possesses one chiral center, racemic form contains equal amounts of two enantiomeric forms i.e., the S and R optical isomers. The biologically active form of Montelukast sodium is the R stereoisomer. Hence it becomes imperative to minimize the formation of S isomer in the commercial product and comply the standards for related substances set by ICH [The international Conference on Harmonization of Technical Requirements for registration of Pharmaceuticals for Human Use. Accordingly, the amount of S optical isomer of Montelukast should be lower than
0.15%.

WO 2006/008750 [Assignee: Matrix Laboratories Limited] discloses novel compounds Methyl 2-[(3 S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl-3-halopropyl]benzoate wherein, ethyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-Y1)ethenyl]phenyl-3-hydroxy propyl]benzoate is reacted with thionyl chloride is MDC. The claimed process involves suspending ethyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl-3-hydroxy propyl]benzoate initially in toluene and heating the reaction contents to 80 °C for 15 min.

In solubles are filtered and contents are heated at reflux to carry out azeotropic distillation at 108-112°C. The reaction mass is cooled to 60°C and concentrated under reduced pressure to get residue. The obtained residue is dissolved in MDC followed by addition of DMF. The reaction contents were cooled to 10°C followed by addition of thionyl chloride slowly and maintaining the reaction temperature at 20-25 °C for 2 hrs. Reaction mass is concentrated under vacuum followed by addition of acetonitrile to the residue at 40 °C. The reaction contents were stirred at 40-45°C for 30 min. Product is filtered and washed with acetonitrile. Obtained yield is 69.9%

WO 2008015703 [Assignee: Matrix Laboratories Limited] discloses novel primary amine salts of Montelukast and process for the preparation of the same. In this claimed invention, DMF is added to 2-[2-[3S[3-[2-(7-Chloroquinolin-2-yl) ethenyl] phenyl]-3- chloropropyl]phenyl]-2- propanol at 25-35 °C under nitrogen atmosphere. Reaction mass is maintained at room temperature for 10-20 minutes to get a clear solution. Reaction mass temp is raised to 35 °C and charged Cesium Carbonate at 33-35 °C. Reaction mass is maintained at 33-35 °C for 5 - 15 min. 1-(Mercaptomethyl) cyclopropane acetic acid in DMF is added to the above solution at 33-37 °C over 4-5hrs. Reaction mass is maintained at 33-37 °C for 30 minutes and checked for the reaction completion. After completion of reaction, ethyl acetate solution is concentrated under vacuum below 45 °C to get residue. The obtained residue is dissolved in ethyl acetate at about 45°C and cooled the mass to 20-25°C. Isopropyl amine is added to the mass at 20-25°C over 30 minutes. Maintained for 1 hr at 20-25°C and then seeded with pure Isopropyl amine salt. Maintained the mass at 20-25°C for 3-12 hrs n-Heptane is added slowly to the mass at 20-25°C over 30 minutes. Maintained the mass at 20-25°C for 3 - 4hrs, filtered the product to isolate Montelukast isopropyl amine salt. Yield: 96.5%

Isopropyl amine salt of Montelukast is suspended in MDC and DM water at 25-30 °C. pH was adjusted to 4.0-4.5 using IN HC1. After workup ethanolic sodium hydroxide was added to MDC layer. Later MDC was concentrated under vacuum to form sticky mass to which methanol was added to form a clear solution. Methanol was concentrated and added n-heptane to obtain Montelukast Sodium.

Surprisingly the present inventors have found that isolation of starting material and intermediates in mixture of solvents and employing moderate reaction temperatures during isolation has resulted in the enhancement of the stereo selectivity of the intermediates and thereby final product Montelukast sodium can be obtained in high optical purity with improved yield.

OBJECT AND SUMMARY OF THE INVENTION:

The main object of the present invention is to provide an improved process for the preparation of Montelukast sodium.

Another object of the present invention is to provide acid addition salts of Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyllphenyl]-3-halopropyl]benzoates.

In one aspect, the present invention provides an improved process for the preparation of Montelukast comprising the steps of:

a) subjecting Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] pheny 1-3-hydroxy propyl]benzoate to azeotropic distillation using methylene dichloride, concentrating the MDC solution to obtain residue, dissolving the residue in methylene dichloride, adding chlorinating agent, isolating Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate hydrochloride in methanol,

b) reacting the obtained compound of step-a with Grignard reagent in presence of cerium chloride to obtain 2-[2-[3S-[3-[2(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]phenyl]-2-propanol;

c) condensing the product of step-b with l-(mercapto methyl)cyclopropane acetic acid in presence of alkali hydroxide or alkali hydride or carbonates followed by saltification with isopropyl amine;

d) optionally purifying the Montelukast isopropyl amine salt in mixture of solvents; and

e) converting the isopropyl amine salt of Montelukast to Montelukast Sodium.

DETAILED DESCRD7TION OF THE INVENTION:

The present invention relates to an improved process for the preparation of
Montelukast.

As used herein, the term MDC refers to methylene dichloride.

As used herein, the term THF refers to tetrahydrofuran.

As used herein, the term DMF refers to dimethyl formamide.

As used herein, the term IPA refers to isopropyl alcohol.

As used herein, the term SOR refers to Specific Optical Rotation.

Accordingly, as illustrated in Scheme-2, Montelukast is prepared by reaction of Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl) ethenyl] phenyl-3-hydroxypropyl]benzoate with chlorinating agent to give Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate hydrochloride which is further condensed with methyl magnesium chloride activated by cerium chloride to give 2-[2-[3S-[3-[2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]phenyl]-2-propanol which is further reacted with l-(mercapto methyl) cyclopropane acetic acid in presence of base and treated with isopropyl amine to isolate as its salt, optionally purifying the isopropyl amine salt of Montelukast and finally converted to Montelukast Sodium.

Scheme-2

The present invention provides an improved process for the preparation of Montelukast sodium comprising the steps of:

" a) subjecting Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] pheny 1-3-hydroxy propyl]benzoate to azeotropic distillation using methylene dichloride, concentrating the MDC solution to obtain residue, dissolving the residue in methylene dichloride, adding chlorinating agent, isolating Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate hydrochloride in methanol,

b) reacting the obtained compound of step-a with Grignard reagent in
presence of cerium chloride to obtain 2-[2-[3S-[3-[2(2E)-(7-
chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]phenyl]-2-propanol;

c) condensing the product of step-b with l-(mercapto methyl)cyclopropane
acetic acid in presence of alkali hydroxide or alkali hydride or carbonates
followed by salification with isopropyl amine;

d) optionally purifying the Montelukast isopropyl amine salt in mixture of solvents; and

e) converting the isopropyl amine salt of Montelukast to Montelukast Sodium.

In one embodiment of the present invention, Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl) ethenyl] phenyl - 3 -hydroxy propyl] benzoate is reacted with chlorinating agents thionyl chloride, phosphoryl chloride, phosphorous pentachloride, preferably thionyl chloride to give Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl] benzoate hydrochloride.

As per the invention, Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl) ethenyl] phenyl - 3 -hydroxy propyl] benzoate is made moisture free by subjecting to azeotropic distillation using methylene dichloride at reflux temperatures. Solvent is concentrated to get residue.

The obtained residue is treated with methylene dichloride; followed by addition of chlorinating agent such as thionyl chloride slowly at 0 to -5°C. After reaction completion, reaction mass is concentrated under reduced pressure to remove the solvent completely followed by addition of methanol. The precipitated solid was filtered to obtain, 2-[2-[(3S)-[3-[(2E)-(7-Chloro quinolin-2-yl)ethenyl]phenyl]-3-chloro-propyl] phenyl -2-propanol hydrochloride. The mother liquor is concentrated to get thick solid and later suspended in methanol to obtain recovered product.

In WO 2006/008750; Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] phenyl-3-hydroxy propyl] benzoate is suspended in toluene and carried out azeotropic distillation at reflux temperature to obtain residue of anhydrous compound. Now, the obtained residue is dissolved in MDC and reacted with thionyl chloride in presence of DMF at 20-25°C. Product is isolated by suspending the after reaction mass in methanol at 45-50°C. Yield obtained is 69.9%

The present invention involves isolation of 2-[2-[(3S)-[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl]phenyl]-3-chloro- propyl]phenyl-2-propanol as hydrochloride salt. The present invention further employs MDC instead of toluene for dehydration of Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl-3-hydroxypropyl] benzoate. Use of high temperatures [108-110°C] for azeotropic distillation is avoided. High temperatures are avoided thereby possibility of product degradation is reduced. Product is isolated using methanol thereby use of relative costly raw material are avoided. Mother liquor is concentrated and suspended in Methanol to recover 2-[2-[(3S)-[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl]phenyl]-3-chloro-propyl]phenyl-2-propanol thereby obtaining maximum yield. Hence the present process has improvements in using relatively cheaper raw materials resulting in reducing costing for the product with improved chiral purity [Specific Optical Rotation >94%].

In another embodiment, Methyl2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] phenyl]-3-chloropropyl] benzoate hydrochloride is treated with sodium hydroxide using MDC and water followed by concentration to obtain Methyl2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] phenyl]-3-chloropropyl]benzoate. In another reaction vessel THF and cerium chloride were suspended and maintained at reflux 10 min to 5 hrs, preferably 3 hrs. Grignard reagent, methyl magnesium chloride or methyl magnesium bromide preferably methyl magnesium chloride was added to the cerium chloride mass at low temperatures such as -5°C to 3°C over a period of 60-90 min. to the activated Grignard reagent, Methyl2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] phenyl]-3-chloropropyl] benzoate was added slowly and maintained the reaction at 5°C to 0°C 25-35°C. After completion of reaction, 2-[2-[(3S)-[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl]phen-yl]-3-chloro-propyl]phenyl-2-propanol is isolated using toluene.

In WO 2006/008751, cerium chloride is suspended in THF and refluxed for 3 hrs. Reaction mass is cooled to -3°C followed by addition of Grignard reagent methyl magnesium chloride at -5 to 0 °C. Reaction is maintained for 2 hrs. Product is isolated using ethyl acetate. Yield of the obtained product 65 %.

The present invention provides treating the Methyl 2-[(3S)-[3-[(2E)-(7-
chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate hydrochloride with
base such as sodium hydroxide by adjusting the pH. Later the chloro compound is
reacted with methyl magnesium chloride and cerium chloride to form 2-[2-[(3S)-
[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl]phenyl]-3-chloro-propyl] phenyl-2-
propanol. Use of toluene for extraction and for isolation renders the process cost-effective resulting in improvement of chiral purity.

In another embodiment, 2-[2-[(3S)-[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl] phenyl]-3-chloro-propyl]phenyl-2-propanol is suspended in a solvent such as dimethyl formamide, added base such as cesium carbonate. Solution of 1-(mercaptomethyl) cyclopropane acetic acid in DMF was added to the reaction mass slowly. After reaction completion, product is extracted into ethyl acetate and concentrated to obtain Montelukast as residue.

The obtained residue is suspended in ethyl acetate and added isopropyl amine to the solution. The isolated solid is treated with toluene to obtain Montelukast isopropyl amine salt.

In another embodiment, Montelukast isopropyl amine salt is optionally purified by suspending crude compound in solvent or mixture of solvents selected from isopropyl alcohol, ethyl acetate, toluene, acetone, isopropyl ether preferably mixture of isopropyl alcohol and acetone.

As per the present invention, crude Montelukast isopropyl amine salt is suspended in solvent mixture of isopropyl alcohol and acetone at 50-55°C followed by cooling and stirring to isolate Montelukast isopropyl amine with enhanced chiral purity. The purification step is optionally repeated to obtain the desired chiral purity.

In another embodiment, Montelukast isopropyl amine is neutralized in the presence of acid such as hydrochloric acid in a solvent such as methylene dichloride followed by solvent removal to get residue and to which ethanolic sodium hydroxide solution is added and Montelukast Sodium is isolated using n-heptane.

The present invention is illustrated below with few-non limiting examples.

Example 1: Preparation of Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl) ethenyl] phenyl]-3-chloropropyl] benzoate hydrochloride Step-l:Methyl-2-[3(S)-[3-[2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-hydroxy propyl] benzoate (100 gm) was suspended in methylene dichloride (600 ml) and temperature was raised and maintained at reflux for about 15 min. The solution was dehydrated by azeotropic distillation at temperature 35-40°C for about 60-90 min. Solvent was concentrated under reduced pressure at 35-40°C to obtain residue.

Step-2: The above obtained residue was dissolved in methylene chloride (600 ml) at 25 - 35°C. Solution was cooled and thionyl chloride (51.90 g) was slowly added at 0°C to -5°C, the temperature of the reaction mass was raised and maintained at 0°C to 2°C for 3 hrs. Reaction mass was concentrated under vacuum at temperature below 35°C. Fresh methanol (1500 ml) was added to the mass at 2 5-35 °C. Temperature of the mass was raised to 50-55°C and stirred for 30 min. solid was filtered and dried.

Mother liquor was concentrated to get thick solid and suspended in a reaction vessel containing acetonitrile (38 ml). Reaction mass was concentrated to get thick solid. Methanol (450 ml) was added to the solid. Temperature was raised to 50-55°C and stirred for 30 min. The reaction mass was cooled slowly over 1 hr to 25-35 and stirred for 60 min. The reaction mass was further cooled to 3-5°C and maintained for 60 min. The obtained solid is filtered and washed with methanol. Chiral Purity: 92-94%

Example 2: Preparation of 2-[2-[(3S)-[3-[(2E)-(7-Chloroquinolin-2-yl)ethenyl]phenyl]-3-chloro-propyl]phenyl-2-propanol Step-1: MDC (300 ml) and DM water (300 ml) were taken into a reaction vessel and product of example 1 (100 gm) was added at 25-35°C. pH was adjusted to 7.0 - 9.0 with sodium hydroxide solution and maintained for 10-15 min at 25-35°C. Layers were separated and to aqueous layer were extracted with MDC (200 ml). Combined organic layers were concentrated under reduced pressure to obtain solid which was later cooled and added THF (100 ml) at 25-35°C.

Step-2: THF (800 ml) was taken in a reaction vessel and charged Cerium chloride (57 gm) under nitrogen atmosphere. Contents were cooled to 0 to -5°C and added methyl magnesium chloride (280 gm) slowly at 0 to -5°C over 90 min. Reaction mass was maintained for about 1 hrs. The above Step-1 material was added slowly and maintained for 60 min at 0-5°C. After completion of reaction, mass was quenched into a pre-cooled (below 0°C) reaction vessel containing DM water (800 ml); acetic acid ( 110 g); toluene (500 ml). Temperature was raised to 20-25°C and stirred for 60 min at 20-25°C. Aqueous layer was extracted twice with toluene (400 ml) at 20-25°C. Combined organic layers were subjected to washings with sodium carbonate solution; sodium chloride solution. The organic layer was subjected to carbon treatment and distilled off the solvent completely under reduced pressure to obtain thick solid. To the solid obtained, toluene (400 ml) was added and heated to 80-85°C and stirred for 15 min. Mass was further cooled and filtered. Yield: 65-70 g; Chiral purity: 92-95%

Example 3: Preparation of Montelukast Isopropyl amine

DMF (500 ml) was taken into a reaction vessel along with product of example-2 (100 gm) at room temperature under nitrogen atmosphere. Contents were stirred at RT for 10-20 min. Temperature was raised to 35 °C and added cesium carbonate (205.3 gm) at 35 °C. Reaction was maintained for 10 min at 35°C. Meanwhile 1-(mercaptomethyl) cyclopropane acetic acid (33.7 gm dissolved in 200 ml of DMF) was added slowly over 1-3 hrs at 35-37 °C. Reaction was maintained for 30 min at 33-37°C until completion. Reaction contents were cooled to 25-30 °C and quenched into a reaction vessel containing ethylacetate (1000 ml); 5% sodium chloride solution (1000 ml) below 30 °C. Layers were separated and aqueous layer was extracted with ethyl acetate (1000 ml). Both the organic layers were combined and subjected to washings with tartaric acid solution and sodium chloride solution. The organic layer was dried over anhydrous sodium sulphate and treated with carbon. Filtered mass was subjected to distillation under reduced pressure to get residue.

Ethyl acetate (500 ml) was added to the obtained residue and maintained at about 45°C for 10-20 min to dissolve under nitrogen atmosphere. Mass was cooled to 15-20°C and to this mono isopropyl amine (12.5 gm) was added slowly over 30-60 min at 20-25°C. Reaction contents were stirred for 12-24 hrs at 20-25°C. Toluene (1000 ml) was added under nitrogen atmosphere and maintained for 1 hr at 15-20°C. Temperature was raised to 50-55°C and maintained for 1 hr. Reaction mass was cooled to 15-20°C and maintained for 10 hrs. Obtained solid was filtered to get Montelukast isopropyl amine salt. Yield: 90-100 g; Chiral purity: 92-95%

Example 4: Purification of Montelukast Isopropyl amine salt IPA (200 ml) and acetone (400 ml) were taken into a reaction vessel at 25-35°C and raise the reaction temperature to 45-50 °C. Product of example-3 (100 gm) was added under nitrogen atmosphere at 45-50 °C. Reaction was maintained at 45-50 °C for about 90-120 min followed by cooling of the mass to 15-20 °C.

Reaction mass was stirred for 4hrs at 15-20 °C. Reaction mass was filtered to get wet cake of Montelukast which is transferred into another reaction vessel. The process of adding solvent mixture of IP A and acetone, heating the contents to 45-50 °C, maintaining for 2 hrs; cooling and stirring for 4 hrs at 15-20 °C and finally filtration was optionally repeated to obtain Montelukast isopropyl amine with desired chiral purity. Yield: 50-60 g; Chiral Purity: 99.9%

Example 5: Preparation of Montelukast Sodium

MDC (2000 ml) was taken in a reaction vessel and charged Montelukast isopropyl amine of example-3 (100 gm) at 25-35 °C under nitrogen atmosphere. DM water (1000 ml) was added; followed by cooling and adjusting the pH of the mass to 4.0-4.5 using IN HC1 at 10-15 °C. The organic mass was extracted into MDC and dried over anhydrous sodium sulphate. To the obtained layer, 323 ml of 0.486 M ethanolic sodium hydroxide solution was added and treated with carbon. The contents were filtered and filtrate was distilled off to get thick mass. Methanol (1000 ml) was added and heated to 35-40 °C. Clear solution was obtained and concentrated under reduced pressure. n-Heptane (100 ml) was added and concentrated under reduced pressure to get solid. The obtained solid is made free by adding n-heptane (2000 ml) at 25-35 °C in nitrogen atmosphere. Product is filtered and dried under inert conditions to Montelukast Sodium pure.

Yield: 90-95 g; Chiral purity: 99.9-99.95%

We claim:

1. An improved process for the preparation of Montelukast sodium
comprising the steps of:

a) subjecting Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl] pheny 1-3-hydroxy propyl]benzoate to azeotropic distillation using methylene dichloride, concentrating the MDC solution to obtain residue, dissolving the residue in methylene dichloride, adding chlorinating agent, isolating Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate hydrochloride in methanol;

b) reacting the obtained compound of step-a with Grignard reagent in presence of cerium chloride to obtain 2-[2-[3S-[3-[2(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]phenyl]-2-propanol;

c) condensing the product of step-b with l-(mercapto methyl)cyclopropane acetic acid in presence of alkali hydroxide or alkali hydride or carbonates followed by salification with isopropyl amine;

d) optionally purifying the Montelukast isopropyl amine salt in mixture of solvents; and

e) converting the isopropyl amine salt of Montelukast to Montelukast Sodium.

2. The process according to claim 1, wherein the chlorinating agent used in step-a is thionyl chloride, phosphoryl chloride, phosphorous pentachloride.

3. The process according to claim 1, wherein the Grignard reagent used in the step-b is selected from methyl magnesium chloride or methyl magnesium bromide.

4. The process according to claim 1, wherein the alkali hydroxide used in the step-c is sodium hydroxide.

5. The process according to claim 1, wherein the Montelukast isopropyl amine salt is purified in mixture of solvents selected from isopropyl alcohol, ethyl acetate, toluene, acetone, isopropyl ether.

6. The process according to claim 5, wherein Montelukast isopropyl amine salt is purified in mixture of isopropyl alcohol and acetone.

7. Acid addition salt of Methyl 2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]benzoate.

8. The compound according to claim 7, wherein the acid is hydrochloride.

9. A process for the preparation of Montelukast sodium substantially as herein described with reference to the foregoing examples.