FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION :
AN IMPROVED PROCESS FOR THE PREPARATION OF ESZOPICLONE
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS : Wockhardt Limited, D4-MIDC Area, Chikalthana,
Aurangabad - 431 210 (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The invention provides an improved process for the preparation of
eszopiclone.
The following specification particularly describes the invention and the manner
in which it is to be performed.

4. DESCRIPTION
The invention provides an improved process for the preparation of eszopiclone.
Eszopiclone, is chemically known as (+)-(5S)-6-(chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b] pyrazin-5-yl-4-methyl- piperazine-1-carboxylate and is represented by formula I.


N-CH,

Formula I
Eszopiclone, marketed under the name LUNESTA, is a non-benzodiazepine hypnotic, indicated for the treatment of insomnia and is the more active dextrorotatory isomer of zopiclone.
There are several patents and patent applications, which discloses process for the preparation of eszopiclone or salts thereof such as U.S. Patent No. 6,444,673, U.S. Patent No. 7,125,874, U.S. Patent Application No. 2007/054914, U.S. Patent Application No. 2007/203145, International (PCT) Application No. 2006/136866, International (PCT) Application No. 2007/088073 and International (PCT) Application No. 2007/083188.
The inventors have now developed a process for the preparation of eszopiclone. The eszopiclone is produced when an eszopiclone salt is treated with a base in presence of a solvent. The eszopiclone produced by this process has a specific optical rotation (SOR, [a]D25) of 138 ± 3° (c = 1% acetone) and chiral purity of 99.0% or more.

In one aspect of the invention there is provided a process for the preparation of eszopiclone wherein the process includes steps of:
a) treating eszopiclone salt with a base in presence of solvent and
b) isolating eszopiclone base from the reaction mixture thereof
The process of invention involves treating eszopiclone salt with a base such as sodium hydroxide in a mixture of water and an organic solvent at a temperature of 20-40 °C and at a pH of about 7-11. The organic layer is separated and concentrated to obtain a residue. The residue was redissolved in organic solvent such as acetonitrile in hot condition. After getting clear solution the reaction mixture was cooled to 25-30 °C and eszopiclone was isolated.
In general, the eszopiclone so formed has specific optical rotation (SOR, [a]D25) of 138 ± 3° (c = 1% acetone) and chiral purity of 99.0% or more.
In this disclosure specific optical rotation ([a]D25) refers to the angle of rotation of plane polarized light at 25 °C with the sodium D line when plane-polarized light is passed through a sample with a path length of 1 decimeter and a sample concentration of 1 gram per 1 deciliter.
The base include from the group of sodium hydroxide, potassium hydroxide, magnesium hydroxide, ammonium hydroxide and the like; carbonate salts such as sodium carbonate, potassium carbonate and magnesium carbonate.
The non-limiting examples organic solvent include carbon tetrachloride, chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, diethyl ether, ethyl acetate, heptane, hexane, methyl-tert-butyl ether, pentane, toluene and 2,2,4-trimethylpentane or a mixture thereof.
In this disclosure, eszopiclone salt refers to salts zopiclone with a chiral acid. The chiral acids include from the group of L-tartaric acid, D-tartaric acid, di-p-anisoyl-D-tartaric acid, Di-p-toluyl-D-tartaric acid, dipivaloyl-D-tartaric acid, D-tartaric acid


momoparachloro anilide, dibenzoyl-D-tartaric acid monodimethyl amide, D-lactic acid, D-malic acid, (S)-2-methoxy phenyl acetic acid, (R)-2-methoxy-2-trifluoromethyl phenylacetic acid, D-mandelic acid, S-hydratropic acid, S(+)-1,1'-binaphthalene-2,2'-dihydrogen phosphate, 1S-10-camphor sulfonic acid, N-acetyl-l-aspartic acid (and other N-protected amino acids), (R)-(+)-1,1'-bis-napthol, (+)-camphoric acid, D-glucuronic acid.
The present invention is further illustrated by the following example which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example
Preparation of eszopiclone base:
Eszopiclone tartrate (4.0 g) was dissolved in a mixture of dichloromethane (40 ml) and water (40 ml) and adjusted the pH to 11 using 2N aqueous sodium hydroxide solution at 20-25 °C. The layers were separated and organic layer was washed with water (25 ml X 2). The organic layer was concentrated to obtain residue and the residue was redissolved in acetonitrile (18 ml) in hot condition. After getting clear solution the reaction mixture was cooled to 25-30 °C for 1 hour and eszopiclone was isolated from the reaction mass thereof. Yield: 1.8 g
SOR [c =1%, acetone]: 139°. Chiral purity: 99.93%.


We Claim:
1. A process for the preparation of eszopiclone wherein the process comprises
steps of:
a) treating eszopiclone salt with a base in presence of solvent and
b) isolating eszopiclone base from the reaction mixture thereof.

2. The process of claim 1, wherein a base is selected from the group of sodium hydroxide, potassium hydroxide, magnesium hydroxide, ammonium hydroxide and the like; carbonate salts such as sodium carbonate, potassium carbonate and magnesium carbonate.
3. The process of claim 1, wherein the solvent is mixture of water and an organic solvent.
4. The process of claim 3, wherein an organic solvent comprises of carbon tetrachloride, chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, diethyl ether, ethyl acetate, heptane, hexane, methyl-tert-butyl ether, pentane, toluene, 2,2,4-trimethylpentane or a mixture thereof.
5. The process of claim 1, wherein eszopiclone has a [a]D25 = 138 ± 3° (c = 1% acetone).
6. The process of claim 1, wherein eszopiclone has a chiral purity of 99.0% or more.
Dated this _TH day of DECEMBER, 2007

Abstract
The invention provides an improved process for the preparation eszopiclone.