FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"A PROCESS FOR THE PREPARATION OF OSPEM1FENE"
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17th Floor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada, Navi Mumbai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

A PROCESS FOR THE PREPARATION OF OSPEMIFENE FIELD OF THE INVENTION:
The present invention relates to a commercially viable process for the preparation of ospemifene.
BACKGROUND OF THE INVENTION:
Ospemifene is chemically defined as (Z)-2-[4-(4-chloro-l, 2-diphenyl-but-l-enyl) phenoxy] ethanol and is represented by compound of structural formula I.

Formula I
Ospemifene is one of the main metabolite of toremifene and is known from Kangas, Cancer Chemother. Pharmacol. (1990) 27:8-12;
Ospemifene is an estrogen agonist and antagonist sold in USA under the proprietary name of "OSPHENA" and is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
U.S. Patent No. 5,750,576 describes a process for the preparation of ospemifene compound of structural formula I as shown below in scheme no. I.

U.S. Patent No. 7,812,197 describes a process for the preparation of ospemifene compound of structural formula I as shown below in scheme no. II.

Drugs & Clinic, Year 2012, Issue 4, Page 351-352 describes a process for the preparation of ospemifene compound of structural formula I as shown below in scheme no. IV.

There is a need for the commercially viable synthetic process for the preparation of ospemifene compound of structural formula I. Accordingly the present invention provides a commercially viable alternative process for the preparation of ospemifene compound of structural formula I.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide a commercially viable process for the preparation of ospemifene compound of structural formula I.
A second aspect of the present invention is to provide a process for the preparation of ospemifene compound of structural formula I comprises the steps of reacting compound of structural formula VIII with compound of structural formula XI to get ospemifene compound of structural formula I.

X = CI, Br, I, mesyloxy, tosyloxy or any other good leaving group
Another aspect of the present invention is to provide a process for the preparation of ospemifene compound of structural formula I comprises the steps of reacting compound of structural formula VIII with compound of structural formula XI in presence of base in an organic solvent to get ospemifene compound of structural formula I.
X = CI, Br, I, mesyloxy, tosyloxy or any other good leaving group
Another aspect of the present invention is to provide a process for the preparation of ospemifene compound of structural formula I as shown below in scheme no. III.

X = CI, Br, I, mesyloxy, tosyloxy or any other good leaving group Scheme III

DETAIL DESCRIPTION OF THE INVENTION:
The compound of formula VIII used herein may be prepared by the processes known in the art such as those described in U.S. Patent No.7,812,197 which is incorporated herein by reference only.
The compound of structural formula XI used herein may include but not limited to 2-bromoethanol compound of structural formula XII.
Formula XII
The reaction of compound of formula VIII with compound of structural formula XI may be carried out in presence of base in an organic solvent to get ospemifene compound of structural formula I.
The examples of base may be selected from the group comprising of inorganic base or organic base.
The examples of inorganic base may include but not limited to hydroxides alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide etc., carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or sodium hydride etc.
The examples of organic base may include but not limited to triethyl amine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), dimethyl amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or l,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc.

The examples of an organic solvent may include polar aprotic solvents or mixture(s) thereof.
The polar aprotic solvents may be selected from the group comprising of tetrahydrofuran, glycol dimethylether, methyl tert-butyl ether, diglycoldimethyl ether, dimethylformamide, N-Methyl-2-pyrrolidone, dimethylacetamide, dimethyl sulfoxide, nitromethane, acetonitrile, ethyl acetate or mixrure(s) thereof.
The reaction of compound of formula VIII with compound of structural formula XI may be carried out at a temperature in the range of 25°C to 110°C.
The reaction of compound of formula VIII with compound of structural formula XI may be carried out for a period of 30 minutes to 8 hours.
The ospemifene compound of structural formula I may be isolated by quenching the reaction mixture with water followed by extracting with above mentioned polar aprotic solvent or non-polar organic solvents. The resulting organic layer was dried over sodium sulphate and concentrated under reduce pressure to get ospemifene compound of structural formula I.
The examples of non-polar organic solvent may include but not limited to toluene, dichloromethane, chloroform, diethyl ether etc.
The isolated ospemifene compound of structural formula I may be dried at a temperature in the range of 40°C to 50°C for a period of 1 hour to 6 hours.
EXAMPLES:
In the following example, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way

Example 1: Preparation of ospemifene compound of structural formula I.
A solution of (Z)-4-(4-chloro-l, 2-diphenylbut-l-enyl) phenol compound of formula VIII (10 gm) in dimethylformamide (140 ml) was added potassium carbonate (6.2 gm) and stirred for 1 hour at 100°C. The resulting reaction mixture was added solution of 2-bromoefhanol compound of structural formula XII (7.4 gm) in dimethylformamide (140 ml) at 100°C and stirred for 5 hours at 100°C. Then reaction mixture was cooled to 25-30°C, quenched with water (300 ml) and extract with ethyl acetate (2x100 ml) to get organic layer. The resulting organic layer was dried over sodium sulphate (50 gm) and concentrated under reduce pressure to get solid. The resulting solids were dried at 40-45°C for 3 hours to get title compound. Yield: 11.2gm Purity: 99.8% (By HPLC)

WE CLAIM:
1. A process for the preparation of ospemifene compound of structural formula I comprises
the steps of reacting compound of structural formula VIII with compound of structural
formula XI to get ospemifene compound of structural formula I.
X = CI, Br, I, mesyloxy, tosyloxy or any other good leaving group
2. The process according to claim no. 1, wherein reaction of compound of formula VIII with compound of structural formula XI is carried out in presence of base in an organic solvent to get ospemifene compound of structural formula I.
3. The process according to claim no. 2, wherein the examples of base is selected from the group comprising of inorganic base or organic base.
4. The process according to claim no. 3, wherein the examples of inorganic base is selected from the group comprising of hydroxides alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide etc., carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or sodium hydride etc., the examples of organic base is selected from the group comprising of triethyl amine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), dimethyl amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or l,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc.

5. The process according to claim no. 2, wherein the examples of an organic solvent is selected from the group comprising of polar aprotic solvents such as tetrahydrofuran, glycol dimethylether, methyl tert-butyl ether, diglycoldimethyl ether, dimethylformamide, N-Methyl-2-pyrrolidone, dimethylacetamide, dimethyl sulfoxide, nitromethane, acetonitrile, ethyl acetate or mixture(s) thereof.
6. The process according to claim no. 1, wherein the reaction of compound of formula VIII with compound of structural formula XI is carried out at a temperature in the range of 25°C to ll0°C.
7. The process according to claim no. 1, wherein the reaction of compound of formula VIII with compound of structural formula XI is carried out for a period of 30 minutes to 8 hours.
8. A process for the preparation of ospemifene compound of structural formula I as shown below in scheme no. III.

9. A process for the preparation of ospemifene compound of structural formula I as herein described with reference to the examples and drawings accompanying this specification.