FORM 2THE PATENT ACT 1970(39 of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rulel3)
1. TITLE OF THE INVENTION:PURIFICATION PROCESS FOR RANOLAZINE PIPERAZINEINTERMEDIATE
2. APPLICANT (S)(a) NAME: WOCKHARDT LTD.(b) NATIONALITY: INDIAN(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra (East),Mumbai-400 051.
3. PREAMBLE TO THE DESCRIPTIONThe present invention relates to a process for purification of 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, as a key ranolazine intermediate.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention relates to a process for purification of 1-[(2,6-dimethyl phenyl)aminocarbonylmethyl]piperazine, as a key ranolazine intermediate.
Ranolazine of Formula I, is chemically 1-piperazineacetamide, N-(2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-,(±) and it is indicated for the treatment of chronic angina.

U.S. Patent No. 4,567,264 discloses racemic (±)-N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl].The '264 patent further discloses the process for purification of ranolazine intermediate, 1-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine using hexane.
European application EP483932 A1 discloses the use of 1 -(2-methoxyphenoxy)-3-aminopropan-2-ol as an intermediate for ranolazine preparation.
PCT application WO2006008753 disclosed polymorphic Form A of Ranolazine, and process for the same.
The process for purification of ranolazine intermediate, 1-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine, using hexane leads to a product having static charge. More over the product isolated from hexane is contaminated with the dimer impurity of formula II.
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The present inventors have surprisingly found a process for purification 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, ranolazine intermediate using an organic solvent selected from aromatic hydrocarbon, ether and mixtures thereof. The product so obtained has negligible static charge and reduced dimer impurity.
In one aspect of the present invention there is provided a process for purification of ranolazine intermediate, 1-[(2,6-dimethylphenyl)aminocarbonylmethyl] piperazine compound of formula III. The process includes step of,

a) adding 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine to an organic solvent selected form aromatic hydrocarbon, ether and mixtures thereof.
b) stirring the resultant mixture to about 20-100 ° C;
c) isolating pure 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine from reaction mass thereof.
The non limiting examples of aromatic hydrocarbon, ether includes xylene, toluene, chlorobenzene, nitrobenzene, methyl tert-butyl ether (MTBE), tertiary
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amyl methyl ether (TAME), tertiary hexyl methyl ether (THEME), ethyl tertiary butyl ether (ETBE), tertiary amyl ethyl ether (TAEE), diisopropyl ether (DIPE) and mixtures thereof.
In another aspect of the present invention there is provided ranolazine intermediate, 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, having not more than 10000 ppm of dimer impurity of formula II.
In another aspect there is provided a process for purification of ranolazine intermediate 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, wherein the said intermediate has purity of 99 % or more.
The 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine so obtained is coupled with epoxy propane intermediate under reflux to obtain ranolazine or salts thereof.
While the present invention has been described in terms of its specific embodiments, 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.
Examplel :Purification of 1-f(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine.
The 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine was suspended in toluene. The reaction mixture was heated to about 90 °C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at 8-12 °C for about 1 hour. The crystallized material was filtered and dried to obtain the title compound. Purity by HPLC: 99.4 %
Example2:Purification of 1-r(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine.
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The 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine was suspended in MTBE. The reaction mixture was stirred to about 30-55 °C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at 8-12 °C for about 1 hourr. The crystallized material was filtered and dried to obtain the title compound. Purity by HPLC: 99.0%
Example3:Purification of 1-f(2.6-dimethylpheny)aminocarbonylmethyl]piperazine.
The crude [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride was suspended in MTBE and toluene solvent system. The reaction mixture was stirred to about 55°C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at 8-12 °C for about 1 hourr. The crystallized material was filtered and dried to obtain the title compound. Purity by HPLC: 99.2 %
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WE CLAIM:
1. A process for purification of ranolazine intermediate 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine compound of formula III. The process comprising,

Formula III
a) adding 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine to an organic solvent selected from aromatic hydrocarbon, ether and mixtures thereof;
b) stirring the resultant mixture to about 20-100 ° C;
c) isolating pure 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine from reaction mass thereof.

2. The process of claim 2, wherein the aromatic hydrocarbon, ether includes xylene, toluene, chlorobenzene, nitrobenzene, methyl tert-butyl ether (MTBE), tertiary amyl methyl ether (TAME), tertiary hexyl methyl ether (THEME), ethyl tertiary butyl ether (ETBE), tertiary amyl ethyl ether (TAEE), diisopropyl ether (DIPE) and mixtures thereof.
3. The process of claim 1, wherein the solvent is toluene.
4. The process of claim 1, wherein the solvent is MTBE.
5. The process for purification of ranolazine intermediate, 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, according to claim 1, has purity of 99 % or more by HPLC.
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6. The ranolazine intermediate, 1-[(2,6-dimethylphenyl)aminocarbonylmethyl] piperazine, having not more than 10000 ppm of dimmer impurity of formula II.

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Abstract
The present invention relates to a process for purification of 1-[(2,6-dimethyl phenyl)aminocarbonylmethyl]piperazine, as a ranolazine intermediate.