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 INTERMEDIATE
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 [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride, as a 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 [(2,6-di methyl phenyl) -aminocarbonylmethyl]chloride, as a ranolazine intermediate.
Ranolazine of Formula I, is chemically 1-piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-,(±) and it is indicated for the treatment of chronic angina.

Formula I
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 [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride using hexane.
European application EP483932 A1 discloses the use of 1-(2-methoxyphenoxy)-3-aminopropan-2-ol as an intermediate in ranolazine preparation.
PCT application WO2006008753 disclosed polymorphic Form A of Ranolazine, and process for the same.
Process for purification of ranolazine intermediate, [(2,6-dimethylphenyl)-amino carbonylmethyl]chloride using hexane is not suitable at industrial scale. More over the product isolated from hexane has having a dark brown color and significant static charge.
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The present inventors have surprisingly found a process for purification of [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride, a ranolazine intermediate using one or more of a polar solvent. The process is simple at commercial scale, and the product so obtained has better purity and negligible static charge.
In one aspect of the present invention there is provided a process for purification of ranolazine intermediate, [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride compound of formula II. The process includes step of,

Formula II
a) adding [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride to one or more of a polar solvent;
b) stirring the resultant mixture to about 20-100 ° C;
c) isolating pure [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride from reaction mass thereof.
In another aspect the solvent of step a), comprises both a polar protic and aprotic solvent either alone or in combination. The non limiting examples of polar solvent includes one or more of n-butanol, isopropanol, n-propanol, ethanol, methanol, 1,4-dioxane, tetrahydrofuran, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, methyl isobutyl ketone (MIBK), methyl ethyl ketone and the like.
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In another aspect there is provided a process for purification of ranolazine intermediate [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride, wherein the product has purity of 99 % or more.
The [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride is coupled with piperazine to get [(2,6-dimethylphenyl)-aminocarbonylmethyl]piperazine, which is coupled with epoxy propane intermediate under reflux to get 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.
Example 1: Purification of r(2.6-dimethylphenyl)-aminocarbonylmethyl]chloride.
The [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride was suspended in IPA. The reaction mixture was stirred to about 80 °C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at about 15 °C for about 2-3 hours. The crystallized material was filtered and dried to obtain the title compound.
Purity by HPLC: 99.2 %
Example 2: Purification of [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride.
The [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride was suspended in acetone. The reaction mixture was stirred to about 30-50 °C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at about 15 °C for about 2-3 hours. The crystallized material was filtered and dried to obtain the title compound.
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Purity by HPLC: 99.0%
Example 3: Purification of r(2,6-dimethylpheny]-aminocarbonylmethyl]chloride.
The [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride was suspended in acetonitrile and IPA solvent system. The reaction mixture was stirred to about 80 °C so as to obtain a clear solution. The resultant mixture was subjected to cooling and maintained at about 15 °C for about 2-3 hours. The crystallized material was filtered and dried to obtain the title compound.
Purity by HPLC: 99.0 %
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WE CLAIM:
1. A process for purification of ranolazine intermediate, [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride compound of formula II. The process comprising,

Formula II
a) adding [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride to one or more of a polar solvent;
b) stirring the resultant mixture to about 20-100 ° C;
c) isolating pure [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride from reaction mass thereof.

2. The process of claim 1, wherein the solvent is selected from the group comprising of polar protic solvent, polar aprotic solvent and mixtures thereof.
3. The process of claim 2, wherein the solvent is selected from the group comprising one or more of n-butanol, isopropanol, n-propanol, ethanol, methanol, 1,4-dioxane, tetrahydrofuran, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, methyl isobutyl ketone (MIBK), methyl ethyl ketone and the like.
4. The process of claim 1, wherein the solvent is isopropanol.
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5. The process for purification of ranolazine intermediate, [(2,6-dimethylphenyl)-aminocarbonylmethyl]chloride, according to claim 1, has purity of 99 % or more by HPLC.

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