FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"AN IMPROVED PROCESS FOR PREPARING 2-[3-CYAN04-(2-
METHYLPROPOXY)PHENYL]-4-METHYLTHIAZOLE-5-CARBOXYLIC
ACID AND ITS CRYSTALLINE FORM-G"
2. APPLICANT:
(a) NAME: HARMAN FINOCHEM LIMITED
(b) NATIONALITY: Indian Company incorporated under the
Companies Act, 1956
(c) ADDRESS: 107, Vinay Bhavya Complex, 159-A, C.S.T. Road, Kalina,
Mumbai - 400098, 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 INVENTION:
The present invention relates to an improved, economical and advantageous process for preparing 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid (formula-1) and its crystalline form-G.
BACKGROUND OF INVENTION:
2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout, which is sold under the brand name Uloric.

2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazoIe-5-carboxylic acid and its pharmaceuticalllly acceptable salts are first disclosed in US 5,614,520. Process for preparing 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid described in US'520 includes reduction of 2-(4-isobutyloxy-3-nitrophenyl)-4-methyl-5-thiazole carboxylate with Pd/C in presence of ethanol and ethylacetate which was further treated with sodium nitrile solution and neutralized with sodium bicarbonate solution. Diazotization followed by cyanation with cuprous cyanide and potassium cyanide to form2-(3-cyano-4-isobutoxyphenyI)-4-methylthiazole-5-carboxylate which further hydrolyzed with sodium hydroxide in presence of ethanol and tetrahydrofuran to give 2-[3-cyano^4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid (Scheme-1).


Scheme-1
Japanese patentsJP3202607 and JP2834971also disclose process for preparing 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methyIthiazole-5-carboxylic acid through cyano intermediate.
WO 2012073259 provides a process for preparation of 2-[3-cyano-4-(2-methy[propoxy) phenyl]-4-methylthiazole-5-carboxylic acid using carboxamide derivative of 2-(4-hydroxyphenyl)-4-methyl thiazole.
US 6,225,474 discloses polymorphic forms A, B, C, D, G, amorphous form of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid and preparation methods of polymorphic forms and amorphous form.
WO 2012131590 describes process for preparation of polymorphic form C of 2-[3-cyano-4-(2-methyIpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid.
Crystalline form H1 and H2 of 2-[3-cyano-4-(2-methylpropoxy) phenyI]-4-methylthiazole-5-carboxylic acid were disclosed in WO 2010038971.

WO 2012168948 discloses crystalline form H3 and H4.
WO 201107911 Al discloses crystalline form R of2-[3-cyano-4-(2-methyIpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid. WO 2008067773 discloses crystalline Form H, I and J of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid. WO 2012048861 discloses form-III of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylicacid.
The prior art processes reported for preparation of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methyIthiazole-5-carboxylic acid involve use of hazardous metal cyanides and Pd/C which is environmentally harmful and uneconomical.
Therefore, there is a need in the art to develop safe, improved, economical and industrially applicable process for the preparation 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid and its crystalline form-G with high purity and high yield.
SUMMARY OF THE INVENTION:
The present invention discloses an improved process for preparation of 2-[3-cyano_,4-(2-methylpropoxy) phenyl]-4-methy!thiazole-5-carboxy!ic acid of formula-] and its crystalline form-G.

In one aspect, the present invention provides the insitu process for preparing 4-hydroxy benzothioamide of formula-4 which comprises

(a) reacting 4-hydroxy benzaldehyde of formula-2


with hydroxylammonium chloride in presence of polar aprotic solvent at 90-150°C to form 4-hydroxy benzonitrile of formula-3

(b) further reacting formula-3 with thioacetamide in presence of mineral acid at an elevated temperature to form 4-hydroxy benzothioamide of formula-4 and
(c) isolating 4-hydroxy benzothioamide of formula-4.
In another aspect the present invention provides process for preparing ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-],3-thiazole-5-carboxylate of formula-7 which comprises


(a) reacting 4-hydroxy benzothioamide of formula-4 with alk.yI-2-halo acetoacetates of formula-5;

in presence of organic solvent to give ethyl-2-(4-nydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate of formula-6 at temperature of 50-85°C; and

formylating formula-6 with hexamethylene tetra amine in presence of mineral acids at50-85°C to isolate ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyi-l,3-thiazole-5-carboxylate of formuIa-7.ln a further aspect the present invention provides method for preparing ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate of formu!a-8 which comprises

(a) reacting ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate of formula-7 with hydroxylammonium chloride in presence of polar aprotic solvent or mixture of two or more polar aprotic solvents at 50-95°C to obtain

ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxy!ate of
formula-8;
(b) precipitating formula-8 in water and
(c) Purifyingformula-8 in water immiscible solvent.
In another aspect the present invention provides process for preparing crude2-[3-cyano_,4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula-1, which comprises;
(a) alkylating ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-
carboxylate of formula-8 in presence of alkylating agent, inorganic base and polar
aprotic solvent at 30-75°C to form ethyl-2-(3-cyano-4-(2-
methylpropoxy)phenyl)-4-methyl-l,3-thiazole-5-carboxylate of formula-9 and

(b) Hydrolysing the formula-9 in presence of inorganic base and organic solvent at 30-75°C to form crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula-1.
In another aspect the present invention provides a process for purification of crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula 1 which comprises:
(a) dissolving crude2-[3-cyano-4-(2-methyIpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid in an organic solvent at elevated temperature followed by treatment with charcoal and

(b) isolating pure 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid.
In a further aspect the present invention provides a process for preparing crystalline form-G of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid which comprises:
(a) dissolving 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid in an organic solvent at elevated temperature;
(b) stirring and gradually cooling to an ambient temperature;
(c) adding water to precipitate Form-G and
(d) Filtering obtained product.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention describes an improved process for preparing 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of (Formula-1) and its
crystalline form-G.

In a preferred embodiment the invention discloses insitu process for preparing 4-hydroxy benzothioamide which comprises:
(a) reacting 4-hydroxy benzaldehyde of formula-2 with hydroxylammonium chloride in presence of polar aprotic solvent to form 4-hydroxy benzonitrile of formula-3;
(b) reacting formula-3 with thioacetamide in presence of mineral acid to form 4-hydroxy benzothioamide of formuIa-4 at an elevated temperature and

(c) lsolatingformula-4 in water.
In the above process the polar aprotic solvent used in step-a is selected from N,N-dimethyl formamide, N,N-dirnethyl acetamide and Dimethyl sulfoxide. Step (a) is carried out at temperature range of 90-150°C.
The mineral acid used in step-b is selected from orthophophoric acidor Polyphosphoric acid that serves as a solvent as well as acidic media. The elevated temperature as referred above in step (b) ranges between 50-85°C.
The HPLC purity of 4-hydroxy benzothioamide thus obtained is in the range of 93-96%.
The said process is described in reaction scheme-2 given below:

In another embodiment, the invention discloses a process for preparing ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-tniazole-5-carboxylate from 4-hydroxy benzothioamide which comprises:
(a) reacting 4-hydroxy benzothioamide of formula-4 with alkyl-2-haloacetoacetate of formula-5 in presence of organic solvent to give ethyI-2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxyIate of formula-6;
(b) formylatingformula-6 with Hexamethylenetetra amine in presence of two or more mineral acids as a solvents to form ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate of formula-7and
(c) isolating formula-7from water.
TheaIkyl-2-haloacetoacetate(where halo = CI, Br, I and alkyl= methyl, ethyl, propyl, butyl etc.) ispreferablyEthyl-2-chloroacetoacetate.

The organic solvent used in step-a is selected from alcohols such as Denatured alcohoI(herein after "DNS") DNS with 0.5-50% Ethyl acetate, DNS with 0.5-50% Toluene, DNS with 0.5-50%Acetone, DNS with 0.5-50% Morpholine or mixture of them, other alcohols like Methanol, Propanol, Isopropanol, n-Butanol.
Formylation is carried out in presence of mineral acids such as Orthophosphoric acid, Poly phosphoric acid as solvents.
According to the above process, the reaction is carried out at temperature of 50-85°C.
The HPLC purity of ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylateof formula -7 thus obtained is in the range of 96-99%.
The process of the above embodiment is given in scheme-3.


In another embodiment the invention discloses a method for preparing ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate from ethy!-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate which comprises:
(a) reacting ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate of formula-7 with hydroxylammonium chloride in presence of polar aprotic solvent or mixture of two or more polar aprotic solvents to obtain ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxy late of formula-8;
(b) precipitatingformula-8 in water and
(c) purifying formula-8 in water immiscible solvent.
In the above embodiment tbe polar aprotic solvent is selected from Dimethyl sulfoxide, acetonitrile, N,N-dimethyl formamide, N,N-dimethyl acetamide. The reaction temperature ranges between 50-95°C for said process.
The water immiscible solvent is selected from the group consisting of Ethyl acetate, Carbon tetrachloride, Chloroform, Butanol, Cyclohexane, 1,2-dichloroethane, Dichloromethane, Ethyl ether, Heptane, Hexane, Methyl-t-butyl ether, Methyl ethyl ketone, Pentane and Toluene.
The HPLC purity of ethyl-2-(3-cyano-4-hydroxyphenyI)-4-methyI-l,3-thiazole-5-carboxylate of formula-8 thus obtained is in the range of 95-98%.
The reaction scheme of the above embodiment is given below in scheme-4.


In a further embodiment the invention provides a process for preparing 2-[3-cyano^4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid from ethyI-2-(3-cyano-4-hydroxyphenyI)-4-methyl-1,3-thiazole-5-carboxylate which comprises
(a) alkylating ethyl-2-(3-cyano-4-hydroxyphenyI)-4-methyl-l,3-thiazole-5-carboxy!ate of formula-8 in presence of alkylating agent, inorganic base and polar aprotic solvent to form ethyl-2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-l,3-thiazole-5-carboxylate of formula-9;
(b) purifyingformula-9 in ketone as solvent and
(c) hydrolyzing formula-9 in presence of inorganic base and organic solvent to form crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula-1
In the above embodiment the alkylating agent is Isobutyl bromide. The inorganic base is selected from Carbonate salts of alkali and alkaline earth metals like Potassium carbonate, Potassium bicarbonate, Sodium carbonate, Sodium bicarbonate, Cesium carbonate, Calcium carbonate. The temperature ranges between 30-75°C for the said process.
The organic solvent is selected from alcohols such as Denatured alcohol(herein after "DNS") DNS with 0.5-50% Ethyl acetate, DNS with 0.5-50% Toluene, DNS with 0.5-50% Acetone, DNS with0.5-50% Morpholine or mixture of them, other alcohols like Methanol, Propanol, Isopropanol, n-Butanol. The ketone is selected from Acetone, Methyl ethyl ketone, Diethyl ketone, Methyl-t-butyl ketone, Isopropyl ketone.
The HPLC purity of crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula I thus obtained is in the range of 98.5-99.5%.
The reaction scheme for said process is given in scheme-5.


Scheme-5
In another embodiment the invention provides a process for purification of crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic which comprises:
(a) dissolving 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazoIe-5-carboxylic acid in an organic solvent at elevated temperature followed by treatment with charcoal and
(b) isolating pure 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid.
In the above process the organic solvent is selected from alcohols such as Denatured alcohol(herein after "DNS") DNS with 0.5-50% Ethyl acetate, DNS with 0.5-50% Toluene, DNS with 0.5-50% Acetone, DNS with 0.5-50% Morpholine or mixture of them, other alcohols like Methanol, Propanol, Isopropanol, n-Butanol. The elevated temperature ranges between 45-85°C for the said process.
The HPLC purity of pure 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid thus obtained is in the range of 99.6-100%.
In a further embodiment the invention provides a process for preparing crystalline form-G of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid which comprises:
(a) dissolving 2-[3-cyano-4-(2-methylpropoxy) phenyI]-4-methylthiazo!e-5-carboxylic acid in an organic solvent at elevated temperature;
(b) stirring and gradually cooling to an ambient temperature; and
(c) adding DM water to isolate the product.
The organic solvent is selected from the group consisting of alcohols such as Denatured alcohol(herein after "DNS") DNS with 0.5-50% Ethyl acetate, DNS with 0.5-50% Toluene, DNS with 0.5-50% Acetone, DNS with 0.5-50% Morpholine or mixture thereof

other alcohols like Methanol, Propanol, lsopropanol, n-Butanol. The elevated temperature ranges between 45-85°C. The ambient temperature ranges between 15-45°C.
The HPLC purity of crystalline form-G thus obtained is in the range of 99.6-100%.
The crystalline form-G of 2-[3-cyano-4-(2-methyIpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid characterized by XRD which matches with disclosed form-G in US patent 6,225,474.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
Examples:
Example-l: Preparation of 4-hydroxy benzothioamide
To the stirred solution of 200ccdimethylformamide and 0.84 mole 4-hydroxy benzaldehydeadded0.78 mole hydroxylamine hydrochloride and heated the reaction mass up to 90-150°C and stirred for 4-8 hrs at same temperature and after completion of reaction distilled out solvent. Then reaction mass was cooled to 25-35°C and added 150cc ortho phosphoric acid and stirred for 10-30 min at ambient temperature. Added 1.02 mole thioacetamide at room temperature and temperature was rised to 50-85°C and stirred for 4-9 hrs, after completion of reaction, cooled the reaction mass to 25-55°C and isolated the product with the addition of water to obtain 80% 4-hydroxy benzothioamide.
HPLC PURITY: 93-96%
Example-2: Preparation of ethyl-2-(4-hydroxyphenyi)-4-methyl-l,3-thiazole-5-carboxylate
To the 400cc DNS (0.5-50% ethyl acetate) added 0.65 mole 4-hydroxy benzothioamide and stirred the reaction mass for 10-40 min at 20-3 5°C then added solution of 0.68mole ethyl 2-chloro acetoacetate in lOOcc DNS within 30-90min at 20-35°C.The reaction mass was stirred for 3-6hrs at 55-85°C. After completion of the reaction, the reaction mass was cooled to ambient temperature and stirred for 30-60min and further cooled to 0±5°C and

stirred for l-3hrs then filtered the reaction mass to obtainethyl-2-(4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate with 85% yield.
HPLC PURITY: 98-99.5%
Example 3: Preparation of ethyl-2-(3-formyl-4-hydroxyphenyl)-4-inethyl-l,3-thiazole-5-carboxylate
To the stirred mixture of 150cc ortho phosphoric acid and 400cc poly phosphoric acid added 0.38 mole ethyI-2-(4-hydroxyphenyI)-4-methyl-l,3-thiazoIe-5-carboxylate at 25-45°C within a period of 2-5hrs. After completion of addition, temperature of the reaction mass rised up to 55-85°C andadded0.45 mole hexa methyl tetra amine within a period of 30-90min and reaction mass was stirred for 4-8hrs at 55-85°C.After completion of reaction, the product was isolated from water and further purified in methanol to obtain 82%ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazoIe-5-carboxylate.
PURITY BY HPLC: 96-99%
Example-4: Preparation of ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate.
To the600cc mixture of DMSO and ACN (acetonitri]e)added 0.98mole ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylateand stirred for 10-30min and temperature was rised to 55-95°C; then added 0.41 mole hydroxyl amine hydrochloride and stirred for 4-9hrs at 55-95°C.After completion of reaction, the product was precipitated in water and purified in 500cc ethyl acetate at 25-55°C to obtain 72% yield of ethyI-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylate.
PURITY BY HPLC: 95-98%
Example-5: Preparation of ethyl-2-(3-cyano-4-(2-methylpropoxy) phenyI)-4-methyl-l,3-thiazole-5-carboxylate
To the stirred mixture of 300cc dimethyl formamide and 0.68 mole potassium carbonate,added 0.34 mole of ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxylateand temperature of the reaction mass was rised to 45-115°C then added

0.57 mole isobutyl bromide in lOOcc DMF within 30-150 min at 50-90°C.After the completion of addition, the reaction mass was stirred for 5-9hrs at 45-115°C.After the completion of the reaction, cooled reaction mass to 25-75°C and isolated the product from water and further purified from acetone to obtain75% ethyl-2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-l,3-thiazoIe-5-carboxylate.
HPLC PURITY: 98-99.5%
Example 6: Preparation of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxyIic acid
To the stirred mixture of 700cc DNS (0.5-50% ethyl acetate) and 0.29 mole ethyl-2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-l,3-thiazole-5-carboxylate added 0.37 mole sodium hydroxide in 300cc water at 0-25°C within 30-180 min; after completion of addition, the temperature of the reaction mass rised to 35-75°C and stirred for 2-5 hrs. After completion of the reaction, the reaction mass was cooled to 0-25°C; acidified with dil. hydrochloric acid solution. The reaction temperature was rised to 75-85°C;charged 100 cc Tetrahydrofuran and further stirred for 2-4 hrs at 25-40°C and isolated the product to obtain crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methyIthiazole-5-carboxyIic acid.
HPLC PURITY: 98.5-99.5%
Example 7: Purification of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid
Dissolved 0.31 mole of crude 2-[3-cyano-4-(2-methylpropoxy) phenyI]-4-methylthiazole-5-carboxyIic acid in 700cc DNS (0.5-50% ethyl acetate) at temperature 45-85°C.Added 5% charcoal and stirred for 15-50min at same temperature and filtered through hyflo and collected the filtrate and charged 100 cc Tetrahydrofuran. The reaction mass was stirred for 30-90 min at 45-85°C then gradually cooled to 0-25°C and stirred for another 2-4hrs and isolated the product to obtain pure 2-[3-cyano^4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxyIicacid.
HPLC PURITY: 99.6-100%
Example VIII:

Preparation of Form-G
Dissolving0.31 mole of crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazoIe-5-carboxylic acid in 700cc DNS (0.5-50% ethyl acetate) at temperature of 45-85°C.Stirred for 30-90 min and gradually cooled to 15-45°C and added 700ccwater within 60-120min at 25-45°C and stirred for 2-4hrs at same temperature and filtered the product to obtain Form-G of 2~[3-cyano-4-(2-methylpropoxy) phenyI]-4-methylthiazole-5-carboxylic acid.
HPLC PURITY: 99.6-100%

We claim,
1. An improved process for preparing 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid of formula-1

comprising:
(a) reacting 4-hydroxybenzaldehyde insitu with hydroxylammonium chloride in presence of polar aprotic solvent at a temperature range 90-150°C to form 4-hydroxy benzonitrile followed by reacting with thioacetamide in presence of mineral acid as a solvent at a temperature range 50-85°C to form 4-hydroxy benzothioamide;
(b) reacting 4-hydroxy benzothioamide with ethyl 2-chloro aceto acetate in presence of organic solvent to give ethyI-2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxy late;
(c) formylating ethyl-2-(4-hydroxyphenyI)-4-methyl-l,3-thiazole-5-carboxylate in presence of hexa methyl tetra amine, mixture of two or more mineral acids to obtain ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-l,3-thiazole-5-carboxyIate;
(d) reacting ethyl-2-(3-formyl'4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate with hydroxy! amine hydrochloridein presence of one or more polar aprotic solventsto give ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyI-l,3-thiazole-5-carboxylate;
(e) alkylating ethyl-2-(3-cyano-4-hydroxyphenyl)-4-memyl-l,3-thiazole-5-carboxylate in presence of alkylating agent, inorganic base and polar aprotic solvent to give ethyl-2-(3-cyano-4-(2-methyIpropoxy)phenyl)-4-methy 1-1,3-thiazole-5-carboxy late;

(f) Hydrolyzing ethyl-2-(3-cyano-4-(2-methylpropoxy) phenyl)-4-methyl-l,3-thiazole-5-carboxylate in presence of inorganic base and organic solvent to obtain crude 2-[3-cyano-4-(2-methylpropoxy) phenyI]-4-methylthiazole-5-carboxyIic acid and optionally
(f) purifying crude 2-[3-cyano-4-(2-methyIpropoxy) phenyI]-4-methylthiazole-5-carboxylicacid.
2. The process according to claim 1, wherein the reaction temperature for step (b)
is 50-85°C.
3. The process according to claim 1, wherein, the polar aprotic solvent is selected
from the group consisting of N,N-dimethyl formamide, N,N-dimethyl acetamide, Dimethyl sulfoxide, AcetonitrNe.
4. The process according to claim 1, wherein the mineral acid is selected from
Orthophophoric acid and Polyphosphoric acid.
5. The process according to claim 1, wherein the inorganic base in step-f is
selected from the group consisting of carbonate salts of alkali and alkaline earth metals like potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, calcium carbonate preferably potassium carbonate.
6. A process for purification of crude 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-
methylthiazole-5-carboxylic acid according to claim I comprising:
(a) Dissolving 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acidin an organic solvent at elevated temperature followed by treating with charcoal and
(b) Isolating pure 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid.

7. An improved process for preparing 2-[3-cyano-4-(2-methylpropoxy) pheny]]-4-
methylthiazole-5-carboxyIic acid in crystalline form-G comprising:
(a) Dissolving pure 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid in an organic solvent at elevated temperature;
(b) Stirring and gradually cooling to an ambient temperature;
(c) Adding water and
(d) Isolating the product.
8. The process according to claims 6&7, wherein, the organic solvent is selected
from the group consisting of alcohols such as Denatured alcohol(herein after "DNS"), DNS with 0.5-50% Ethyl acetate, DNS with 0.5-50% Toluene,DNS with 0.5-50% Acetone, DNS with 0.5-50% Morpholine or mixture thereof other alcohols like Methanol, Propanol, Isopropano! and n-Butanol.
9. The process according to claim 7, wherein the elevated temperature ranges
between 45-85°C and an ambient temperature ranges between 15-45°C.
10. The process according to any of the preceding claims, where in purity of 2-[3-
cyano-4-(2-methylpropoxy) phenyl]-4-methyIthiazole-5-carboxylic acid is
99.6-100%.