FORM 2

THE PATENTS ACT, 1970;
[39 Of 1970]
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION: [SECTION-10; RULE 13]
AN IMPROVED PROCESS OF THE RESOLUTION OF RACEMIC ZOPICiONE
CENTAUR CHEMICALS PRIVATE LIMITED, a Company incorporated under companies Act, 1956, having registered office at Centaur House, Shantinagar, Vakola, Sanalacruz (E), Mumbai.- 400 055, State of Maharashtra, India
The following specification particularly describes the invention and the manner in which it is to be performed:

Field of Invention:
The present invention relates to an improvement in the process of (S)-(+)-6-(5-chloro-2-pyridyl)-5-{4-methyH -piperazinyl arbonyloxy]-7-0x0-6, 7-dihydro-5H-pyrazolo [3,4-b] pyrazine, also known by the name Es-zopicione.
Background of Invention:
(+)- Zopiclone, chemically named as 6-(5-chloro-<2-pyridyl)-5-[4-
methyl-1 -piperazinyl cdrbonyloxyJ-7-oxo-6,7-dihydro-5H-
pyrazolo [3,4-b] pyrazine, is a hypnotic agent of cyclopyrrolone class possessing a pharmaceutical profile similar to that of benzodiazepines with high efficiency and low toxicity. The $-(+)-enantiomer of zopiclone is less toxic and more active than its other enantiomer.

The enqntiomers of zopiclone can be separated by crystallization of corresponding diastereoisdmer salts obtained with optically active acids- For example, {+) or (-) malic acid (Chirality, 1993,5,419) or (+) -O, 0'~ dibenzoyl tartaric acid (EP Patent 609210 - B1) can be used as chiral acids.
In Tetrahedron Asymmetry, 1997,8,995, ES, patent 2101653, US Patent 6969767 Bl, the preparation of (+) - zopiclone is described

from an optically active carbonate, which in turn obtained by enzymatic resolution of a racemic mixture. ,
Prior Art
The process disclosed in the EP 60921 OBI for resolution of Zopiclone comprises steps of -
a) reaction of racemic zopiclone with {+)- 0,0' -dibenzoyl tartaric acid in methylene chloride solvent to obtain diastereomeric dibenzoyl tartaric acid salt;
b) recrystallisation of diastereomeric dibenzoyl tartaric acid salts from acetonitrile (44 parts) followed by two recrystallizations from 17 volumes of methylene chloride - acetonitrile mixture (ratio 47:53) with overall yield of 36%; and (
c) isolation of Es-zopiclone from dibenzoyl tartaric acid salt and recrystallization from acetonitrile to obtain 23% Es-zopiclone.
The main disadvantages of the prior art are::
1) Use of large volume of solvents including mixture of solvents.
2) Use of acetonitrile for final purification, which forms solvate with Es-zopiclone, which is very difficult to remove during drying process.

Objective of Invention:
The present invention describes the cost effective, environment friendly process for preparation-of Es-zopiclone from racemic zopiclone using {+)-0, O'-dibenzoyl tartaric acid.
Summary of Invention
The present invention provides for use of diastereorneric (+)-0, O'-dibenzoyl tartaric acid salt of zopiclone in the preparation of S-zopiclone by simplified industrial resolution process comprising:
a) reacting a solution of racemic zopiclone in organic solvent with (+)-0,0'- dibenzoyl tartaric acid in
organic solvent at temperature ranging 0°C to 60°C for a period ranging between 1 - 24 hours, to obtain zopiclone (+)-0,0'-dibenzoyl tartarate salt;
b)" recrystallisation of dibenzoyl tartarate salt obtained in step (a) in single , organic solvent at a
temperature ranging between 0°C-80°G.; and
c) isolation of Es-zopiclone from desired dextrorotatory dibenzoyl tartarate salt and recrystallization from organic solvent at temperature ranging between
0°C-80°C,
Detailed Description of invention
The process for producing Es-zopiclone from racemic zopiclone is given in Scheme 1.

REACTION SCHEME OP Es-ZOPICLONE MANUFACTURE


CI

H Ov ■ /—\.
zr\ /N_CH*
O v—/ Racemic Zopiclone

f

(+)-2,3-Dibenzoyl-D-tartaric acid
Q"

Es-ZOPICLONE

In accordance with Scheme I, the solution of racemic zopiclone is an organic solvent is treated with (+)-