FORM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention.- PROCESS FOR THE PREPARATION OF
DESOGESTREL
2. Applicant(s)
(a) NAME : LUPIN LIMITED
(b) NATIONALITY : An Indian Company
(c) ADDRESS : 159 CST Road, Kalina, Santacruz (East),
Mumbai-400 098, State of Maharashtra, India
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF THE INVENTION:
The present invention relates to the process for the preparation and purification of
desogestrel.
BACKGROUND OF THE INVENTION:
Desogestrel is chemically known as 13-ethyl-11-methylene-18,19-dinor-l7a-pregn-4-en-20-yn-17-oI and is represented by formula (I).It is a powerful progestogen and widely used in oral contraceptivesin combination with ethinylestradiol.

The methods for the preparation and purification of desogestrel in the prior art documents are discussed below.
The patent US 3,927,046 describes the conversion of compound of formula (II) to desogestrel (I)by reaction with potassium acetylide in THF as solvent and purification of desogestrel by crystallisation from pentane.

The publication Sigfrid et al.,Tetrahedron, 50(36),10709-10720, 1994 discloses the conversion of compound of formula (II) to desogestrel by reaction with lithium acetylide and ethylene diamine in THF as solvent. The crude desogestrel is then purified by crystallisation from n-hexane.

Another publication, Corey et al., Jornal of American Chemical Society, 121, 710-714, 1999 discloses the purification of desogestrel by chromatographic technique using 5% ethylacetate in hexane.
The publication, Compostella et al., Steroids (67), 2002,111-117 discloses the purification of desogestrel from hexane/ethylacetate mixture.
The patent application US 2005/023425 describes the crystallization of desogestrel initially from hexane then followed by from acetone/water.
SUMMARY OF THE INVENTION:
The present invention provides a novel process for the preparation of desogestrel(I), comprising reaction ofll-methylene-18a-homo-estr-4-en-17-one (Il)with acetylene gas in presence of potassium tertiary butoxide and ethylenediaminein dioxane-dimethylacetamide mixtureto give crude desogestrel.
The present invention further provides aprocess for the purification of desogestrel by crystallisation from n-heptane.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention relates to a novel process for the preparation and purification of desogestrel (I).
In one embodiment there is provideda process for the preparation of desogestrel of formula

comprising reaction of compound 11 -methylene- 18a-homo-estr-4-en-17-one of formula (II)
(i)


withaceytylene gas in the presence of potassium tertiary butoxide, ethylenediamine, dioxane and dimethylacetamide mixture as solvent.
The reaction is carried out at temperature in the range of-20 to l00°C, preferably -10 to 50 °C, most preferably 0 to 10 °C.
The ratio of dioxane and dimethylacetamide is 10: 100 to 20:80, more preferably 1:10 to 1:20.
The quantity of dioxane-dimethylacetamide with respect to compound of formula (II) is 10-40 times (weight/volume), preferably 20-25 times (weight/volume).
In another embodiment there is provided a process to obtain pure desogestrel (I) comprising:
i) dissolution of desogestrel in n-heptane by heating,
ii) cooling the solution, and
iii) isolation.
Desogestrel is dissolved in n-heptane by heating upto reflux temperature, preferably in the range of 50 to 60°C.
The solution is initially cooled to 20-30°C then further cooled to 0-5°C.
The pure desogestrel can be isolated by methods known in the literature such as filtration, concentration and evaporation etc.
The pure desogestrel obtained according to the present invention optionally further stirred in methanol or ethanol or mixture thereof.
The purity of desogestrel obtained by the present invention is greater than 99.9%.

The present invention is described in the following examples, however it should be noted that the scope of present invention is not limited by the examples.
EXAMPLE 1:
i) Preparation of potassium acetylide
To a mixture of potassium tertiary butoxide (110g)in dimethyl acetamide (280ml),dioxane (40 ml) was added at 20-30°C and the slurrywas cooled to 2-5°C. Ethylenediamine (12 ml) was added at 2-5 °C. Acetylene gas was purged into the reaction mass at 4-6°C. Stirred for 40 minutes at 10-14°C and then cooled to 2-5°C.
ii) Reaction of potassium acetylide with compound of formula -II
To the solution of compound of formula-II (20g) in dimethylacetamide (100 ml)was added above prepared potassium acetylideat 2-5 °C and stirred for 2-3 hrs. The reaction mass waspoured into mixture of coldwater (1200 ml) and ethyl acetate (500 ml).Acidified to pH 2.5-3.0 using conc, hydrochloric acid (142 ml). The organic layer was washed with water, 10% brine solution and concentrated under vacuum. The residue was chromatographedon silicagel (60-120 mesh size) and eluted with 3.0% ethylacetate/cyclohexane. The fractions containing desogestrel were collected, mixed and concentrated under vacuum to get crude desogestrolyield: 16.8 g
iii) Purification of crude desogestrel:
Themixture of desogestrel (16.8 g)and n-heptane (120 ml) was heated to 53-56°C to get the clear solution.Allowed to cool to room temperatureand stirred for 10-15 hrs. Cooled to 0-5 °Cand filtered the solid. Solid washed with chilled n-hepatane and dried under vacuum. Yield: 12.5 g
HPLC Purity: 99.9%

WE CLAIM:
reaction ofcompound of formula II
1. A process for the preparation of desogestrel of formula I comprising;


withacetylene gas in the presence of potassium tertiary butoxide andethylenediaminein dioxane-dimethylacetamide mixture.
2. The process for preparation of desogestrel according to claim 1, wherein the reaction temperature is between -20 to 100°C, preferably -10 to 50 °C more preferably 0 to 10 °C.
3. The process for preparation of desogestrel according to claim 1, wherein the ratio of dioxane-dimethylacetamide is 10: 100 to 20:80, more preferably 1:10 to 1:20.
4. The process for the preparation of desogestrel according to claim 1, wherein the quantity of dioxane-dimethylacetamide is 10-40 times (weight/volume), preferably 20-25 times (weight/volume).
5. A process to obtain pure desogestrel comprising;
i) dissolution of desogestrel in n-heptane by heating, ii) cooling the solution, and

iii) isolation.
6. The process according to claim 5, wherein the crude desogestrel is dissolved in n-heptane at reflux temperature, preferably at 50- 60 °C.
7. The process according to claim 5, wherein the reaction mass is cooled to 0-5 °C.
8. The process according to claim 5, wherein the pure desogestrel is isolated either by filtration or concentration or evaporation.