FIELD OF THE INVENTION:
The present invention relates to an improved process for the preparation of 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid from l-(prop-l-en-2-yl)-lH-benzo[d]imidazol-2(3H)-one which is used as a key intermediate for the preparation of Zilpaterol. More particularly, the invention relates to an eco-friendly and cost-effective process with shorter reaction time, which provides 4-(l,2-dihydro-2-oxobenzo[d]imidazoI-3-yl)butanoic acid with high yield and purity.
BACKGROUND OF THE INVENTION:
The 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid of formula (I) is a benzimidazole derivative,
H n
CH 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid (Formula-I)
and is one of the key intermediate in zilpaterol manufacturing process.
Zilpaterol code named as RU 42173 is a p2 adrenergic agonist under its trade name Zilmax, it is used to increase the size of cattle and the efficiency of feeding them. Zilmax is produced by Intervet, a subsidiary of Merck & Co., and marketed as a "beef-improvement technology". Zilapterol is chemically represented as 4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino)imidazo[4,5,1 -jk]-[ 1 ]benzazepin-2( 1 H)-one having a structural formula as follows:
H3C
HO VN>
tX>=o
\^~N
H
Zilpaterol
=TtfT fYF F IT F " f H F M W A T fll / "PI S / *? Pi 1 ft" ~1~7 =49

U.S. Patent No. 4,900,735 describes zootechnical compositions of racemic trans Zilpaterol and its derivatives which can be used to increase the rate of weight gain, and improve the feed efficiency and increase carcass leanness in livestock, poultry and fish.
US 2008/0103130 assigned to Pharmacia & Upjohn discloses the preparation of Zilpaterol, and 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid (compound-iv) also known as buzolic acid (in page 7-8), wherein the said intermediate is prepared by multiple steps: by reacting compound-i with 4-Bromobutyric acid methyl ester in presence base K2CO3 and acetone to form ester derivative (compound ii); ester derivative converted to acid derivative (compound-iii) by hydrolyzing in presence of NaOH in THF. Compound-iii is acidified with hydrochloric acid in presence THF to obtain compound-iv.
The process for the preparation of Zilpaterol and it's intermediate preparation has been
disclosed in Edward J. Salaski., Div. Bio-Org. Chem., Inst. Org. Chem., Syntex
Discovery Res., Palo Alto, CA 94304, USA; EN)" Synthesis of
ry—Iinidazpfeervzazepinethiones^A New- Series oLHTV- L, Reyerse-Transcripiase^Inhibitors,
2

Tetrahedron Lett. 36 (1995) 9,. 1387-1390; wherein the said 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid intermediate is prepared by deprotonation of compound-3 with strong base such as sodium hydride in DMF and alkylation of the anion with ethyl 4-bromobutyrate provided die ester compound-4, which was treated with 15% aq NaOH solution in THF to give the acid derivative of compound-5, which is acidified with aq.HCl in presence of DME to produce Compound-6.
The above mentioned routes for preparation of 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid have considerable disadvantages, which involves the use of hazardous chemicals which are harmful to the environment and toxic in nature. Further, the isolation of all the intermediates at different stages of preparation makes the process tedious and leads to low yield.
Considering the short comings in the prior art methods, it is imperative to develop an improved method for the preparation of Zilpaterol intermediate of formula (I), which is cost effective, eco-friendly and high yielding.

The present inventors have now found a much simpler, cost effective process with shorter reaction time when compared to the prior art methods.
OBJECT OF THE INVENTION:
The main object of the present invention is to provide one pot synthesis for the preparation of 4-(l,2-dihydro-2-oxobenzo[d]imida2ol-3-yl)butanoic acid with high purity and improved yield. Another object of the present invention is to provide industrially viable method for the preparation of formula -1 without isolating any intermediates.
SUMMARY OF THE INVENTION:
The main aspect of the present invention is to provide one pot synthesis for the preparation of 4-(l,2-dihydro-2-oxobenzo[d]irnidazol-3-yl)butanoic acid of Formula-1.
The present invention involves condensation of methyl-4-chloro butyrate (formula-Ill) with l-(prop-l-en-2-yl)-lH-benzo[d]imidazol-2(3H)-one of formula - II in presence of a base and suitable solvent to give corresponding ester derivative, which is hydrolyzed in presence of a base and dien acidified with acid to give formula -1.
DESCRIPTION OF THE INVENTION:
The present invention relates to one pot synthesis of 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid of Formula-I, which is used as a key intermediate for the preparation of Zilpaterol.
According to the first embodiment the present invention is to provide one pot synthesis of
4-(l,2-dihydro-2-oxobenzo[d]imidazoI-3-y])butanoic acid intermediate of Formula-I.
u

in presence of base and suitable solvent to obtain ester derivative.
(ii) hydrolysing above ester derivative with base and water to form corresponding salt.
(iii) acidifying the above salt in presence of acid to form 4-(l,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid of Formula-I with 95% yield.
The process is schematically represented as below in Scheme-3:

According to one embodiment of the present invention, the base used in condensation step is an inorganic base.
According to another embodiment of the invention, the base is alkali carbonates, alkali bicarbonate, and alkali hydroxides.
According to yet another embodiment of the invention, the base is potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, preferably potassium carbonate.
According to another embodiment of the invention, the suitable solvent used in condensation step is selected from the group comprising DMSO, Acetonitrile, Acetone, Methyl isobutyl ketone preferably DMSO.
According to another embodiment of the invention, hydrolyzation of ester derivative in presence of base, wherein the base is preferably sodium hydroxide.
According to another embodiment of the invention, hydrolyzation in presence of inorganic solvent, wherein die inorganic solvent is preferably Water.
According to yet another embodiment of the present invention, acidification is carried out in presence of acid selected from HC1, HBr, Phosphoric acid, preferably hydrochloric
acid.
While the present invention has been described in terms of its specific embodiment, 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:
Procedure: To a stirred solution of l-(prop-l-en-2-yl)-lH-beno[d]imidazole-2(3H)-one (100 gm, 0.57 mole) in DMSO (150 ml) was added potassium iodide (1 gm), TBAB (lgm) and potassium carbonate (104 gm, 0.75 mol) and slowly heated to 100°C. Methyl-4-chloro butyrate (120 gm, 0.85 mol) was added lot wise to the above reaction mixture at 100°C for 4-5 hrs. After completion of addition, the reaction mixture was stirred for 8-10 hrs at 110-115°C. After completion of reaction, RM was diluted with water and extracted with chloroform and distilled to get crude compound. Water and sodium hydroxide (57 gm , 1.42 mol) was added to the above obtained crude material and stirred for 6 hrs at 95-100°C and further it was reacted with Cone. HC1 (120 ml) and maintained for 5-6 hrs at 80-85°C. Reaction mixture was cooled to room temperature and obtained precipitate was filtered to get 120 gms of 4-(l,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid as brown color solid. Yield: 95%. HPLC purity- 98%.