COMPLETE AFTER PROVISIONAL LEFT ON 8 NOV 200 5 FORM 2 THE PATENTS ACT, 1970. (39 OF 1970) COMPLETE SPECIFICATION. [See sections 10 and Rule 13] TITLE APPLICANT A METHOD OF PREPARATION 0* LEVOROTATORY [2-[4-[(4-CHLOROPHENYL) -PHENYL METHYL] -1- PIPERAZINYL] ETHOXY] ACETIC ACID DIHYDROCHLORIDE. Praveen Laboratories Private Limited ADDRESS Plot No. 1, Block No. 206, Moje-Jalwa, Tal. Palsana. Dist. Surat. NATIONALITY Indian The following specification describes the nature of this invention and the manner in which it is to be performed: ORGN ORGN 1319/MUM/2005 20.10.05 - 8 NOV 2005 Title A Method Of Preparation Of Levorotatory [2-[4-[(4-ChIorophenyI)-PhenyI Methyl]-1- Piperazinyl] Ethoxy] Acetic Acid Dihydrochloride Background of the invention There has been a significant increase in the number of reported allergic conditions over the last three decades. This is evidenced by the increased levels of antibodies developed in response to environmental allergic factors such as dust mites pets and air pollutants. Cetirizine and its salts, including dihydrochloride is known and is effective in the treatment of allergies including but not limited to chronic and acute allergic rhinitis, allergic conjunctivitis, pruritus, urticaria and the like. Cetirizine is orally active lc.g- acting histamine HI receptor antagonist. Antihistamines such as cetirizine block the effect of histamines that are released by allergic reactions in the body. This mitigates the ability of histamine to promote allergy symptoms. Cetirizine belongs to the second generation of HI histamine receptor antagonists, which are believed to offer significant advantages over first generation compounds. Studies have shown that cetirizine provides safe and effective, symptomatic relief of seasonal allergies. Cetirizine has been shown to provide a positive impact on patients who have experienced activity impairment from allergies thereby significantly improving health related quality of life. Non-sedating character of cetirizine is an important breakthrough in allergy treatment because new generation allergy drugs diminish the commonly experienced sedative effect and allow patients to enjoy an improved quality of life. Cetirizine has an asymmetric center in the molecule and thus may exist as optical isomers (enantiomers). Levocetirizine (structure I A) is the levo rotatory enantiomer of cetirizine. Levocetirizine like cetirizine, has a potential anti-inflammatory effect in the treatment of allergic rhinitis with asthma. Levocetirizine is believed to have a two-fold higher affinity for human HI 2 receptors than cetirizine. Levocetirizine is believed to be rapidly and extensively absorbed. Levocetirizine also has been shown to be free from side effects on the central Nervous system. CI >■—N N CH,CH2OCH2COOH < A^ ■ 2HCI / IA The process for the preparation of levocetirizine and its salt including dihydrochloride is known. For example, GB 2 225 321 A discloses a process for preparation of levocetirizine and its dihydrochloride in which racemic l-[(4-chlorophenyl) phenylmethyl)] piperazine has been resolved by L-tartaric acid to obtain levo rotatory isomer. This isomer is reacted with 2-chloro ethoxy acetonitrile to give nitrile derivative, which is then subjected to hydrolysed and converted into levocetirizine and its dihydrochloride. Tetrahedron Letters 37(28), 4837 (1996), which is incorporated herein by reference, discloses the enantioselective synthesis of optically pure cromium tricarbonyl-benzylic alcohol which converted to levocetirizine in several steps. Opalka C. J. et.al. (Synthesis, 36, 766, (1995)) disclosed (Synthesis 766, 1995) a novel process to prepare the enantiomers of the key intermediate [(-)(1(4- chlorophenyl)phenyi methyl) piperazine (using N,N-Diisopropylethyl amine and 4-Hydroxybenzoic acid) and thus the enantiomers of the antihistamine drug levorotatory 2-(2-{4-[4-Chlorophenyl) phenyl methyl]-1-piperazinyl} ethoxy) acetic acid dihydrochloride in large quantities and in high optical purity. In developing this process, an improved sequence of piperazine formation from an optically pure benzhydrylamine was developed. In addition to providing large scale quantities of the optically pure enantiomers of [(-)( 1(4- chlorophenyl)phenylmethyl) piperazine, these procedures may have general use in the synthesis of related structures. US Patent 5478941 describes Levorotatory and Dextrorotatory enantiomers of l-[(4-Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl) sulfonyl] piperazine of the formula ##STR1## their preparation and use for the preparation of substantially optically pure enantiomers of l-[(4-chlorophenyl)phenymethyl] piperazine, which are themselves valuable intermediate products for the preparation of optically active therapeutic compounds having a very high degree of optical purity. Thus, there are few processes in prior art which describe the preparation of Levocetirizine. However, the several intermediates formed during the synthesis are to be purified, which involves costly catalyst, large excess of solvents adding to the cost of levocetirizine. Also, the utilities associated with the purification method, including the manpower compounds to the production cost. Hence, there is a need to develop the method which can avoid the excess cost and add to the economic benefits. Object of the invention The object of the invention is to provide a novel synthetic method which (a) avoids use of large quantity of the solvents (b) avoids generation of effluent, thus making the process as environment friendly (c) is more economical (d) is less cumbersome and less labour intensive (e) is providing highly chemically pure and (f) is providing levocetirizine with high optical purity. 4 (g) is time saving (h) avoids the isolation of intermediates. Detailed description of the invention The present invention provides the synthetic method Which involves direct conversion of p-chlorobenzophenone (II) to levocetirizine dihydrochloride (I A) by without isolation of any intermediates in a pure form. N^ H CH2CH2OCH2COOH 2HCI (II) (IA) Clemo et al. (J Chem Soc, 1958, (1939)) described a process for the preparation of (-)-4-chlorobenzhydryl amine ( VI ). This process involves formation of tatrate salt ( V ) in water and then kinetic resolution of tartarate salt by crystallization in water for several times. To avoid all these exercises we described here in an alternative solvent system, which gives more pure salt that can achieve required purity after one or two crystallization. NH2 ■ L-tataric acid L-Tartaric acid NaOH (IV) (V) (VI) 5 We have also described here in an alternative process for the synthesis of compound of structure (I) from (-)-4-chlorobenzhydryl amine (VI) and directly from the tartarate salt (V) by using a very economical and easily available chemicals such as NaOH, KOH etc. instead of costly N,N-diisopropyl ethyl amine. NH2 • L-tataric acid NaOH V_/ (V) CIH2C- CIH2C- NaOH NaOH CIH2C- CIH2C- N—Tos N Tos (I) (VI) Thus, according to the present invention, the various intermediates are not purified, with out compromising with the chemical purity as well as optical purity of the final product i.e. levocetirizine. This process • avoids use of the solvents • avoids generation of effluent, thus making the process as environment friendly • more economical 6 • less cumbersome and less labour intensive • providing highly chemically pure and • providing levocetirizine with high optical purity. Experimental Preparation of (-)-4-Chloro benzhydrylamine tartarate salt (Example 1) To a mixture of methanol ( 1185 ml) and water ( 400 ml), 4-Chloro benzhydrylamine ( 200 gm, 0.91 mole ) was added and stir for 10 minutes. To this solution, L-tartaric acid (138 gm, 0.92 mole ) in methanol ( 415 ml) was added drop wise at room temperature during 3-4 hours. After addition completed, the mass was heated to reflux for 1 hour. It was cool to room temperature and stir at this temperature for 6-8 hours. The solid was separated by filtration and washed with water and dried. Dry weight- 138 gm. Melting point - 190°-195°C. Specific optical rotation -Assay by HPLC- 99.1% Preparation of (+) -4-Chloro benzhydrylamine tartarate salt (Example 1) It was made similarly by using tartaric acid instead of L-tartaric acid. Preparation of (-)-l-f(4-Chlrophenvl)phenvlmethyll-4-[(4-methvlphenyl)-sulfonvll piperazine Form (-)-4-Chloro benzhydrylamine tartarate salt. (Example 2) To the solution of NaOH ( 89 gm in 1200 ml of water ), N,N-bis(2-chloroethyl)-4-methyl benzenesulfonamide ( 175 gm, 0.59 mole ) and tartarate salt of (-)-4-Chloro 7 benzhydrylamine ( 200 gm, 0.54 mole ) (prepared as described in example 1 ) added at room temperature. The reaction mixture was stirred at this temperature for 20 minutes and then refluxed for 44 hours. It was cooled to room temperature and solid was separated by filtration, washed with water till neutral pH. It was added to methanol ( 500 ml ) and stirred for 1 hour. The crystals obtained were filtered, washed with chilled methanol and dried. Dry weight - 210 gm. Melting point-165°-167°C. Specific optical rotation - [ °c ] D - 40.75° (c - 1, Toluene) Assay by HPLC - 99.2% Preparation of (+)-l-[(4-Chlrophenvl)phenylmethyl1-4-[(4-methvlphenvl)-sulfonvl1 piperazine Form (+)-4-Chloro benzhydrylamine tartarate salt. (Example 2) It was made similarly by using tartaric salts of (+)-4-chlorobenzhydryl amine. Specific optical rotation [