FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
A PROCESS FOR PREPARATION OF INTERMEDIATE OF
MOXIFLOXACIN
PIRAMAL HEALTHCARE LIMITED, a company incorporated under the Companies Act, 1956, of Piramal Tower, Ganpatrao Kadam Marg, Lower Parel, Mumbai - 400 013, State of Maharashtra, India
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 a process for the preparation of octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine, a key intermediate for the synthesis of l-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid (moxifloxacin) or its pharmaceutically acceptable salts. More particularly, the present invention relates to a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine.
BACKGROUND OF THE INVENTION
Moxifloxacin is chemically known as, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid and structurally represented herein below:

Moxifloxacin is a broad spectrum antibiotic that is active against gram-positive and gram-negative bacteria. It is a fourth generation synthetic fluoroquinolone antibacterial agent, which functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial DNA, thereby inhibiting cell replication. Moxifloxacin hydrochloride is available

worldwide under the brand names Avelox®, Avalox® and Avelon® for oral treatment. In most countries, moxifloxacin or its pharmaceutically acceptable salt is also available in parenteral form for intravenous infusion. Moxifloxacin is also sold as an ophthalmic solution under thebrand name Vigamox® for the treatment of conjunctivitis.
Generally, the process for the preparation of racemic or chiral octahydro-6-
racemic or chiral tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II with a reducing agent such as lithium aluminum hydride (LAH), sodium bis-(2-methoxyethoxy)aluminum hydride commonly known as Vitride® or sodium borohydride/boron trifluoride etherate [NaBH4/BF3.(C2H5)2O] etc. in the presence of a solvent such as tetrahydrofuran, toluene or a mixture thereof to obtain the compound of formula I, a key intermediate in the synthesis of moxifloxcin or its pharmaceutically acceptable salts.
US Patent No. 4,990,517 (hereinafter referred to as US'517 Patent) discloses a process for the preparation racemic octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I. The process comprises catalytic reduction of 6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione using ruthenium on carbon (Ru/C) or palladium on carbon (Pd/C) in the presence of hydrogen to obtain tetrahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II, and subsequent reduction of the compound of formula II using lithium aluminum hydride (LAH) or sodium borohydride boron trifluoride etherate [NaBH4/BF3.(C2H5)2O] as a reducing agent in the presence of about 25.7 volume of absolute tetrahydrofuran as a solvent and stirred the reaction mixture at the boiling point for 10 hours to yield the compound of formula I. The process disclosed in the US'517 Patent necessitates use of lithium aluminum hydride (LAH) as a reducing

agent, which is highly corrosive in nature. Also, LAH on contact with moisture forms lithium hydroxide, which can cause severe burns. The powdered LAH forms dusts that can pose an inhalation hazard. Moreover, the process utilizes large volume of organic solvent, for instance the US'517 Patent requires about 25.7 volume of absolute tetrahydrofuran as a solvent, which renders the process costly and industrially disadvantageous.
The process described in the US'517 Patent is schematically presented herein below:

US Patent No. 5,468,742 (hereinafter referred to as US'742 Patent) discloses a process for the preparation of (4aS,7aS)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine. The process comprises reaction of (4aR,7aS)-tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione with lithium aluminum hydride in the presence of anhydrous tetrahydrofuran at refluxed temperature. The resulting reaction mixture is then cooled and treated with a solution of tetrahydrofuran in water and 10% sodium hydroxide solution to precipitate the. product, (4aS,7aS)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine. The precipitated product was filtered and washed with tetrahydrofuran. The US'742 Patent process discussed herein above suggests use of lithium aluminum hydride as a reducing agent. It is apparent that lithium aluminum hydride is highly corrosive in nature and on contact with moisture forms lithium hydroxide, which can cause

severe burns. Thus, the process for the manufacture of (4aS,7aS)-octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine is industrially nonviable.
US Patent Application Publication No. 20020016462 discloses a process for the preparation of octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I comprising the steps of: (i) reaction of molten tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II at a temperature of 110°C with lithium aluminum hydride as a reducing agent in the presence of mixture of tetrahydrofuran and toluene as a solvent, (ii) the reaction mixture was stirred at a reflux temperature for 5 hours and then cooled the reaction mixture to a temperature of 20°C, (iii) a separately prepared solution of citric acid and sulfuric acid was then charged to the reaction suspension and further stirred at a temperature of 60°C for 1 hour and then cooled to a temperature of 30°C, the pH of the reaction mixture was adjusted to 8.5 using sodium hydroxide solution, (iv) the temperature of the reaction mixture again raised to a temperature of 50°C and stirred for another 1 hour, two layers formed were separated and the separated aqueous layer was extracted at a temperature of 50°C with a mixture of tetrahydrofuran and toluene, (vi) combined all the organic layers and the solvent evaporated under reduced pressure to obtain octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine with 88.1% yield. This process teaches use of lithium aluminum hydride as a reducing agent, which is hazardous in nature. Also, the process requires tedious work up process involving use of citric acid, sulfuric acid etc. for the isolation of octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine from the reaction mixture, thereby rendering the process tedious, lengthy and industrially not applicable.
Indian Patent Application No. 329/CHE/2008 discloses a process for the preparation of octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I,

comprising reaction of tetrahydro-6-(phenylmethyI)-lH-pyrroIo[3,4-b]pyridine-5,7(6H)-dione of formula II with Vitride® as a reducing agent in the presence of toluene as a solvent and heated at a temperature of 27°C to 30°C for 1 hour and further heated at a temperature of 62°C to 67°C for 4 hours. The resulting reaction mixture was then cooled to room temperature and further cooled to a temperature of 0°C to 5°C. To the reaction mixture then added a solution of 20% sodium hydroxide and again heated at a temperature of 55°C for 30 minutes to obtain an organic layer. The resulting organic layer was distilled off to obtain octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine.
However, from the above discussed prior art documents it is clearly evident that, the processes disclosed in the prior art for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I from the racemic or chiral tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II necessitates use of reducing agent such as lithium aluminum hydride (LAH), Vitride® or sodium borohydride/boron trifluoride etherate [NaBH4/BF3.(C2H5)2O], etc in the presence of solvents such as tetrahydrofuran or toluene or a mixture thereof. Thus, there is need to develop a process for the preparation of compound of formula I from the compound of formula II, which is simple, cost-effective, non-hazardous and industrially applicable.
The inventors of the present invention have now found that racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I can be obtained in good yield and high purity using an improved process involving reaction of racemic or chiral tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II with a reducing agent, which is a mixture of dimethyl sulphate and sodium borohydride or a mixture of aluminum chloride and sodium borohydride in the presence of a polar solvent to obtain racemic or chiral

octahydro-6-(phenyImethyl)-lH-pyrrolo[3,4-b]pyridine, a key intermediate in the synthesis of moxifloxacin or its pharmaceutically acceptable salts, which is used as an antibacterial agent.
OBJECTS OF THE INVENTION
An object of the present invention is to provide a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I (the compound of formula I) from racemic or chiral tetrahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II (the compound of formula II).
Another object of the present invention is to provide a process for the preparation racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I with yield of > 74% and purity of > 96%.
Yet another object of the present invention is to provide a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I using non-hazardous reducing agent.
Still another object of the present invention is to provide a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I, which is cost-effective and industrially applicable.
SUMMARY OF THE INVENTION
In accordance with the aspect of the present invention, there is provided a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I comprising reacting racemic or chiral

tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula I, wherein said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1:1 to 1:4.
The process of the present invention is schematically depicted herein below:

In accordance with another aspect of the present invention, the racemic or chiral octahydro-6-(phenyImethyl)-lH-pyrrolo[3,4-b]pyridine of formula I is prepared in yield of > 74% having purity of > 96%.
In accordance with yet another aspect of the present invention, the process for the preparation of compound of formula I overcomes the disadvantages associated with the process disclosed in the cited prior arts, which concerns with the use of hazardous reducing agents, such as lithium aluminum hydride (LAH) or sodium borohydride/boron trifluoride etherate [NaBH4/BF3.(C2H5)2O] and large volume of organic solvents, which renders the process industrially disadvantageous.
In accordance with still another aspect of the present invention, the process for the preparation of compound of formula I from the compound of formula II is carried

out using non-hazardous and simple reducing agent in the presence of relatively less volume of polar solvent, thereby making the process for the preparation of compound of formula I cost-effective, non-hazardous and industrially applicable.
DESCRIPTION OF THE INVENTION
The present invention relates to a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I,

comprising reaction of racemic or chiral tetrahydro-6-(phenylmethyl)-1H-pyrroIo[3,4-b]pyridine-5,7(6H)-dione of formula II,

Formula II
with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula I, wherein said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1:1 to 1:4.

In an embodiment of the present invention, the compound of formula II is reacted with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula I.
In accordance with the embodiment of the present invention, said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1:1 to 1: 4.
In accordance with the embodiment of the present invention, said reducing agent is a mixture of dimethyl sulphate and sodium borohydride.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the mixture of dimethyl sulphate and sodium borohydride as a reducing agent is carried out using 1:1 molar ratio of said dimethyl sulphate to said sodium borohydride.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the mixture of dimethyl sulphate and sodium borohydride as a reducing agent is carried out using said dimethyl sulphate in the mole equivalent of 2 to 8 based on the compound of formula II.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the mixture of dimethyl sulphate and sodium borohydride as a reducing agent is carried out using said sodium borohydride in the mole equivalent of 2 to 8 based on the compound of formula II.
In accordance with the embodiment of the present invention, said reducing agent is a mixture of aluminum chloride and sodium borohydride.

In accordance with the embodiment of the present invention, the reaction of the compound of formula II with the mixture of aluminum chloride and sodium borohydride as a reducing agent is carried out using 1:3 molar ratio of said aluminum chloride to said sodium borohydride.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the mixture of aluminum chloride and sodium borohydride as a reducing agent is carried out using said aluminum chloride in the mole equivalent of 0.5 to 3 based on the compound of formula II,
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the mixture of aluminum chloride and sodium borohydride as a reducing agent is carried out using said sodium borohydride in the mole equivalent of 1 to 5 based on the compound of formula II.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the reducing agent is carried out in the presence of a polar solvent selected from dimethylformamide, tetrahydrofuran, dichloromethane, dimethoxyethane, acetonitrile, dimethylsulfoxide of dimethylformamide or a mixture thereof.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the reducing agent is carried out in the presence of polar solvent is dimethoxyethane or tetrahydrofuran.
In accordance with the embodiment of the present invention, the reaction of compound of formula II with the reducing agent is carried out in the presence of 4 to 10 volume of polar solvent based on the compound of formula II.

In accordance with the embodiment of the present invention, the reaction of compound of formula II with the reducing agent is carried out at a temperature ranging from 20°C to 30°C.
In accordance with the embodiment of the present invention, the racemic and chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I is prepared by reacting the racemic or chiral tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II with a reducing agent in the presence of a polar solvent. The compound of formula I prepared using the process of the present invention is a racemic or a chiral compound of formula I. The racemic or chiral compound of formula I is obtained by reacting appropriately selected racemic or chiral compound of formula II in accordance with the process of the present invention.
In accordance with the embodiment of the present invention, a process for the preparation of racemic octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula Ia comprising reacting racemic tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula IIa with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula Ia, wherein said reducing agent is a mixture of two agents used in a molar ratio ranging from 1:1 to 1:4.


In accordance with the embodiment of the present invention, a process for the preparation of (4aS,7aS)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula Ib comprising reacting (4aR,7aS)-tetrahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula IIb with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula Ib, wherein said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1:1 to 1: 4.

In accordance with the embodiment of the present invention, a process for the preparation of (4aR,7aR)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula Ic comprising reaction of (4aS,7aR)-tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula IIc with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula Ic, wherein said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1 : 1 to 1 : 4.


In accordance with the present invention, the process for the preparation of racemic or chiral octahydro-6-(phenylmethyI)-lH-pyrroio[3,4-b]pyridine of formula I using a mixture of dimethyl sulphate and sodium borohydride as a reducing agent is described herein below:
To a reaction flask charged a solution of sodium borohydride in a polar solvent such as dimethoxyethane or tetrahydrofuran, the suspension formed is cooled to a temperature of 5°C to 10°C. To the reaction mixture is then dropwise added dimethyl sulphate, an evolution of hydrogen gas is observed. The reaction mixture is then warmed to a temperature of 30°C and further stirred for 2 hours. The reaction mixture is then cooled to a temperature of 5°C to 10°C. To the reaction mixture a solution of compound of formula II in a polar solvent is added dropwise and the reaction mixture is warmed to a temperature of 30°C. The reaction mixture further stirred for 18 hours at a temperature of 15°C to 45°C. At this stage the reaction mixture is monitored for the reaction completion using high performance liquid chromatography (HPLC). The starting material in the reaction mixture is not more than (NMT) 3%. The reaction solvent is distilled out and then toluene is charged to the reaction mixture. To the reaction mixture then dropwise added a solution of concentrated hydrochloric acid in water, at this stage fast evolution of hydrogen gas is observed. The reaction mixture is further stirred for 1 hour and heated at a temperature of 80°C to 85°C. Cooled the reaction mixture at a temperature of 25°C to 30°C to precipitate the solid and filtered the solid obtained. The filtrate forms two layers, the organic and aqueous layer, the aqueous layer is separated from the reaction mixture and cooled to a temperature of 5°C to 10°C. The pH of the aqueous layer is adjusted to 12 using sodium hydroxide solution. Then toluene is charged to the reaction mixture and stirred for 15 minutes. Further the two layers formed were separated and the aqueous layer extracted with toluene. All the toluene layers combined together and washed with brine solution. The

toluene layer dried over sodium sulphate and evaporated to dryness to obtain the compound of formula I having yield > 74% and purity > 96%.
In accordance with the present invention, the process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine of formula I using a mixture of aluminum chloride and sodium borohydride as a reducing agent is described herein below:
To reaction flask charged a solution of sodium borohydride in a polar solvent such as dimethoxyethane or tetrahydrofuran and then charged aluminum chloride in lots over a period of time. The reaction mixture is warmed to a temperature of 45°C to 50°C and further stirred for 30 minutes the resulting reaction mixture is cooled to a temperature of 5°C to 10°C and a solution of compound of formula II in a polar solvent is dropwise added to the reaction mixture. The reaction mixture is then warmed to a temperature of 15°C to 45°C and stirred further for 18 hours maintaining the temperature to 15°C to 45°C. The reaction solvent is then distilled out under reduced pressure and cooled the reaction mixture to a temperature of 15°C to 45°C. To the reaction mixture then dropwise added water and distilled out the reaction mixture. Further water is added to the reaction mixture, followed by dropwise addition of concentrated hydrochloric acid over a period of 30 minutes. The reaction mixture is then heated at a temperature of 80°C for 1 hour and then cooled at a temperature of 0°C to 5°C. The solution of sodium hydroxide in water is added to the reaction mixture maintaining the temperature of the reaction mixture below 25°C. Then toluene is charged to the reaction mixture and warmed the reaction mixture to a temperature of 20°C to 30°C with stirring for 15 minutes. The reaction mixture is then filtered and the two layers formed are separated. The aqueous layer is extracted with toluene. All the toluene layers combined together and washed with water and brine solution. The toluene layer dried over sodium

sulphate and evaporated to dryness to obtain the compound of formula I having yield > 74% and purity > 96%.
It is thus possible by the way of the present invention to achieve the much desired process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I with good yield and purity using a cost-effective and industrially applicable process.
The starting material of the present invention, racemic or chiral tetrahydro-6-(phenylmethyI)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II is a known compound and can be prepared by a person skilled in (he art by followrng the process disclosed in the literature. For example, the racemic compound of formula II may be prepared by following the process disclosed in the Indian Patent Application No. 329/CHE/2008, which is incorporated herein by reference. The process involves reaction of pyridine dicarboxylic acid with acetic anhydride followed by treatment with benzyl amine to yield 6-(phenylmethyl)-5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione, which is subsequently reduced using 5% palladium on carbon in the presence of a suitable solvent to obtain the racemic compound of formula II.
Moreover, the chiral tetrahydro-6-(phenylmethyl)-lH-pyrroIo[3,4-bjpyridine-5,7(6H)-dione of formula II may be prepared by following the process disclosed in the US Patent No. 5,468,742, which is incorporated herein by reference. The process involves reaction of cis-tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione with L(+)-tartaric acid as a resolving agent in the presence of ethanol and acetonitrile as a solvent at a reflux temperature to dissolve the reaction material completely, cooled the reaction mixture to a temperature of 50°C and crystallization takes place on addition of seeding crystals. The reaction

mixture was allowed to stand overnight and filter the precipitated crystals to obtain (4aS,7aR)-tetrahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione L-tartrate. The tartrate salt was then dissolved in water and the pH of the reaction mixture was adjusted to 7 to 8 using saturated sodium hydrogen carbonate solution. The aqueous solution extracted four times with methylene dichloride. The combined methylene dichloride layers were dried over magnesium sulphate and concentrated to obtain (4aS,7aR)-tetrahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula IIc.
As previously discussed the compound of formula I, racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine may be further converted to moxifloxacin or its pharmaceutically acceptable salts, which is an antibacterial agent. The compound of formula I obtained using the process of the present invention may be converted to moxifloxacin by following the process described in the cited prior art, Indian Patent Application No. 329/CHE/2008, which is incorporated herein by reference. Mainly, the racemic compound of formula 1a as obtained by the process of the present invention is treated with chiral resolving agent such as D(-)-tartaric acid in the presence of dimethylformamide to obtain (4aS,7aS)-octahydro-6-(phenylmethyl)-1H-p>Trolo[3,4-b]pyridineD(-)-tartrate salt, which is further converted to its free base in the presence of sodium hydroxide or potassium hydroxide and water as a solvent to yield (4aS,7aS)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine. The resulting compound is debenzylated using 5% palladium on carbon in the presence of methanol as a solvent to give (4aS,7aS)-octahydro-lH-pyrrolo[3,4-b]pyridine, which is subsequently treated with cyclopropyl-6,7-diflouro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid in the presence of triethylamine and acetonitrile to obtain moxifloxacin. The moxifloxacin obtained can be further converted to its pharmaceutically acceptable salts.

The following examples which fully illustrate the practice of the preferred embodiment of the present invention are intended to be illustrative purpose only and should not be constructed in any way to limit the scope of the present invention.
EXAMPLES
Example 1: Process for the preparation of compound of formula Ia using mixture of dimethyl sulphate and sodium borohydride as a reducing agent
To a 250ml round bottom flask was charged sodium borohydride (9.3g) dissolved in tetrahydrofuran (80ml), the suspension formed was cooled to a temperature of 5°C to 10°C. Then to the reaction mixture dropwise added dimethyl sulphate (15.2g) and the reaction mixture was warmed to a temperature of 30°C and further stirred for 2 hours. The reaction mixture was then cooled to a temperature of 5°C to 10°C. A solution of compound of formula IIa (10g) in tetrahydrofuran was added to the reaction mixture dropwise and the reaction mixture was then warmed to a temperature of 30°C. The reaction mixture further stirred for 18 hours at a temperature of 20°C to 30°C. The reaction solvent was distilled out and then charged toluene (50ml) to the reaction mixture. Further to the reaction mixture dropwise added concentrated hydrochloric acid (20m|) dissolved in water (40ml). The reaction mixture was stirred for another 1 hour and heated at a temperature of 80°C to 85°C. The reaction mixture was cooled at a temperature of 25°C to 30°C to precipitate the solid and the solid obtained was filtered. The filtrate obtained forms two layers, the aqueous layer was separated from the reaction mixture. The separated aqueous layer was then cooled to a temperature of 5°C to 10°C and the pH of the reaction mixture adjusted to 12 using sodium hydroxide solution. Then charged toluene (50ml) to the reaction mixture and stirred the reaction mixture for

15 min. The two layers formed were separated. The aqueous layer was extracted with toluene. All the organic layers were combined and washed with brine solution. The organic layer was dried over sodium sulphate and was evaporated to dryness to obtain the product. Yield = 84.6% Purity = 99.81%
Example 2: Process for the preparation of compound of formula Ia using mixture of aluminum chloride and sodium borohydride as a reducing agent
To a 1 liter round bottom flask was charged sodium borohydride (27.9g) dissolved in dimethoxyethane (200ml) and to the suspension formed was then charged aluminum chloride (27.9g) in lots over a period of 1 hour. The reaction mixture was warmed to a temperature of 45°C to 50°C and further stirred for 30min. The reaction mixture was then cooled to a temperature of 5°C to 10°C. A solution of compound of formula Ha (60g) in dimethoxyethane (100ml) was added to the reaction mixture dropwise and then warmed the reaction mixture to a temperature of 20°C to 30°C The reaction mixture was further stirred for 18 hours at a temperature of 20°C to 30°C. The reaction solvent was distilled out under reduced pressure and cooled to a temperature of 20°C to 30°C. To the reaction mixture was then added water (280ml) dropwise at a temperature of 20°C to 30°C and distilled out the reaction mixture under reduced pressure. Further water (140ml) was added to the reaction mixture, followed by dropwise addition of concentrated hydrochloric acid (120ml) over a period of 30 min. and the resulting reaction mixture heated at a temperature of 80°C for 1 hour. The reaction mixture was cooled at a temperature of 0°C to 5°C and then charged sodium hydroxide (120g) dissolved in water maintaining the temperature of the reaction mixture below 25°C. Then charged toluene (200ml) to the reaction mixture and warmed the reaction

mixture to a temperature of 20°C to 30°C, further stirred for 15 minutes. The reaction mixture was filtered and the two layers formed were separated. The separated aqueous layer was extracted with toluene. Combined all the organic layers and washed with water and brine solution. The organic layer was dried over sodium sulphate and evaporated to dryness to obtain the product. Yield = 74% Purity = 96%
Example 3: Process for the preparation of compound of formula Ib using mixture of dimethyl sulphate and sodium borohydride as a reducing agent
To a 100ml round bottom flask was charged sodium borohydride (4.8g) dissolved in tetrahydrofuran (40ml), the suspension formed was cooled to a temperature of 5°C to 10°C. Then to the reaction mixture dropwise added dimethyl sulphate (7.8g) and warmed the reaction mixture to a temperature of 30°C and further stirred for 2 hours. The reaction mixture was then cooled to a temperature of 5°C to 10°C. A solution of compound of formula IIb (5g) in tetrahydrofuran was added to the reaction mixture dropwise and the reaction mixture was warmed to a temperature of 30°C. The reaction mixture was further stirred for 18 hours at a temperature of 20°C to 30°C. The reaction solvent was distilled out and then toluene (25ml) was charged to the reaction mixture. Further to the reaction mixture dropwise added concentrated hydrochloric acid (10ml) dissolved in water (20ml). The reaction mixture was stirred for another 1 hour and heated at a temperature of 80°C to 85°C. The reaction mixture was then cooled at a temperature of 25°C to 30°C to precipitate the solid and filtered the solid. The filtrate obtained forms two layers, the aqueous layer was separated from the reaction mixture. The separated aqueous layer then cooled to a temperature of 5°C to 10°C and the pH of the reaction mixture was adjusted to 12 using sodium hydroxide solution. Then charged toluene

(25ml) to the reaction mixture and stirred for another 15 min. The two layers formed were separated. The aqueous layer was further extracted with toluene. All the organic layers were combined and washed with brine solution. The organic layer was dried over sodium sulphate and evaporated to dryness to obtain the product. Yield = 78% Purity = 98.5%
Details for analytical method of analysis:
Apparatus : Gas chromatography with FID and integrator or
comparable system
Column : Capillary column
Separating layer : 14% Cyanopropylphenyl 86% dimethylpolysiloxane e.g.
RTX, Restek
Length : 30m
Internal diameter : 0.25mm
Film thickness : 0.5um
Carrier gas : Hydrogen
Injector temperature : 250°C Detector temperature : 300°C Injection volume : 1μl

WE CLAIM:
1. A process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I (the compound of formula I),

comprising reacting racemic or chiral tetrahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of formula II (the compound of formula
ii),

with a reducing agent in the presence of a polar solvent at a temperature ranging from 15°C to 45°C to obtain the compound of formula I, wherein said reducing agent is a mixture of two reducing agents used in a molar ratio ranging from 1 : 1 to 1 : 4.

2. The process as claimed in claim 1, wherein said reducing agent is a mixture of dimethyl sulphate and sodium borohydride.
3. The process as claimed in claim 1, wherein said reducing agent is a mixture of aluminum chloride and sodium borohydride.
4. The process as claimed in claim 2, wherein the molar ratio of said dimethyl sulphate to said sodium borohydride is 1:1.
5. The process as claimed in claim 2, wherein said dimethyl sulphate is used in the mole equivalent of 2 to 8 based on the compound of formula II.
6. The process as claimed in claim 2, wherein said sodium borohydride is used in the mole equivalent of 2 to 8 based on the compound of formula II.
7. The process as claimed in claim 3, wherein the molar ratio of said aluminum chloride to said sodium borohydride is 1: 3.
8. The process as claimed in claim 3, wherein said aluminum chloride is used in the mole equivalent of 0.5 to 3 based on the compound of formula II.
9. The process as claimed in claim 3, wherein said sodium borohydride is used in the mole equivalent of 1 to 5 based on the compound of formula II.
10. The process as claimed in any one of the preceding claims 1 to 9, wherein said polar solvent is selected from dimethylformamide, tetrahydrofuran, dichloromethane, dimethoxyethane, acetonitrile, dim ethyl sulfoxide or dimethylformamide or a mixture thereof.

11. The process as claimed in claim 10, wherein said polar solvent is dimethoxy ethane.
12. The process as claimed in claim 10, wherein said polar solvent is tetrahydrofuran.
13. The process as claimed in claim 10, wherein said reaction is carried out in the presence of 4 to 10 volumes of polar solvent based on the compound of formula II.
14. The process as claimed in claim I, wherein said reaction is carried out at a temperature ranging from 20°C to 30°C.
15. The process as claimed in claim 1, wherein said compound of formula I is octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine, represented by compound of formula Ia,

16. The process as claimed in claim 1, wherein said compound of formula I is (4aS,7aS)-octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine, represented by compound of formula Ib,


17. The process as claimed in claim 1, wherein said compound of formula I is (4aR,7aR)-octahydro-6-(phenylmethyl)-lH-pyrrolo[3,4-b]pyridine, represented by compound of formula Ic,

18. A process for the preparation of octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formuia I substantially as herein described with reference to examples 1 to 3.