FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
HIGH PURITY BENZIMIDAZOLES AND PROCESS FOR THEIR PREPARATION
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 DESCRIPTION
The present invention provides a process for the preparation of benzimidazoles in high purity and free from solvent.
The following specification particularly describes the invention and the manner in which it is to be performed.
1

4. DESCRIPTION
The present invention provides a process for high purity benzimidazoles free from solvent.
Bezimidazole compounds of Formula I are known for gastric proton pump inhibitors. Several such agents such as lansoprazole wherein R1 and R4 = H, R2 = CH3 and R3 =OCH2CF3, pantoprazole R1 =OCHF2, R2 and R3= OCH3 and R4=H, omeprazole R1 and R3=OCH3, R2 and R4= CH3 and its (S)-enantiomer esomeprazole, laminoprozole and rabeprazole wherein R1 and R4= H, R2 = CH3 and R4= 0(CH)2 O CH3 are known in the art for treating ulcer diseases.

US Patent 6,002,011 discloses the process of crytallising benzimidazole compounds with aqueous alcohol to isolate the water alcohol solvate and desolvate by suspending the solvate in warm water.
EP 302720 discloses the process wherein benzimidazole compound is crystallized from water and ethanol and inevitable contain water and ethanol.
US Application No 2004-0215021 discloses the purification with organic solvent or mixture of organic solvent and water in presence of weak basic gas like ammonia and methylamine.
2

US Patent 6,423,846 disclose the process where crystallization is performed in acetone water and further purification by column chromatography.
The present inventors have noticed that the known processes producing benzimidazoles yield a product where the level of solvent and water is intolerable which frequently do not suit the requirement of formulation. Reducing the level of water and solvent is very time consuming, costly and prolong drying also deteriorates the quality of the final products. The use of column chromatography at commercial scale is not feasible.
While working on the problem of reducing drying time and to obtain the product free from solvent present inventors have now embarked upon a good process of desolvate the benzimidazole compound which employs use of carbon dioxide to produce the bezimidazoles which are solvent and water free.
In one of the aspect of the present invention there is provided a process for preparation of compound of Formula 1

wherein, R1 is selected from group consisting of independently H, OCH3 or OCHF2 ; R2 is selected from group consisting of independently CH3 or OCH3, ; R3 is selected from group consisting of independently OCH3 or OCH2CF3 and 0(CH2)30CH3, R4 is selected from group consisting of independently H and CH3, wherein the said process comprises of,
a) dissolving the compound of formula I in aqueous alkali,
b) isolating the compound of formula I by purging carbon dioxide
3

The bezimidazole of Formula I is dissolved in aqueous alkali such as sodium hydroxide or potassium hydroxide and like. The pH of the reaction mixture is adjusted to around 8 to isolate the product by purging of carbon dioxide followed by isolating the separated benzimidazole of Formula I which on drying under vacuum provides the water and solvent free product.
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 Purification of Lansoprazole
Crude Lansoprazole (750 gm) was dissolved in 10% aqueous ethyl alcohol (6 lit,
1:9) by portion wise addition of solid sodium carbonate (20 gm). The reaction
mixture was heated to 60-70X to get clear solution. The solution was filtered in hot
and filtrate was cooled to 5°C gradually to crystallize out the product. The solid was
filtered and submitted for the purification.
The wet cake obtained was suspended in water (8 Lit) and dissolved by addition of
aqueous sodium hydroxide solution (1 Lit, 8%). The reaction mixture was
charcolized and filtered. Carbon dioxide gas was bubbled slowly to the filtrate to
attain the pH around 8.5. The precipitated solid was filtered, washed and dried to
obtain titled compound in high purity.
Yield: 520 gm
Assay by HPLC: 99.2%
Residual solvent: Not detected
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WE CLAIM:
1. A process for preparation of compound of Formula I

a) wherein R1 is selected from group consisting of independently H, OCH3 or OCHF2; R2 is selected from group consisting of independently CH3 or OCH3; R3 is selected from group consisting of independently OCH3 or CH2CF3 and O(CH2)3OCH3, R4 is selected from group consisting of independently H and CH3 wherein the said process comprises of,
a) dissolving the compound of formula1 in aqueous alkali,
b) isolating the compound of formula I by purging of carbon dioxide.

2. A process according to claim 1 wherein alkali is sodium hydroxide, potassium hydroxide.
3. A process according to claim 1 wherein product of formula I has moisture content less than 0.1%.
4. A process according to claim 1 wherein product of formula I has no residual solvent.
5

5. A process according to claim 1 wherein compound of formula 1 is Lansoprazole.

Dated this 1st day of June, 2006
For Wockhardt Limited

(Yatendra Kumar) Authorized Signatory