IMPROVED PROCESS FOR THE PREPARATION OF (S.S)-2,8-PIAZABICYCLQ[4.3.0]NONANE
FIELD OF THE INVENTION
The present invention is directed to an improved, industrially viable, cost-effective process for the industrial manufacturing of enantiomerically pure (S,S)-2,8-diazabicyclo[4.3.0]nonane of Formula I and its consequent conversion to Moxifloxacin hydrochloride monohydrate.

BACKGROUND OF THE INVENTION
(S,S)-2.8-diazabicyclo[4.3.0]nonane 0f Formula I is an important intermediate in the manufacture of many pharmaceutically active ingredients. Several processes are known in the literature for the preparation of this intermediate.
EP350733 and CA1340553 discloses a process for the preparation of 2,8-diazabicyclo[4.3.0]
nonane which comprises of catalytical hydrogenation of 8-benzyl-5H-pyrrolo[3,4-b]pyridine-5,7(6H)-
dione of Formula II using H2/Ru-C or Pd/C to give 8-benzyl-2,8-Diazabicyclo[4.3.0]nonane-7,9-dione
of Formula III followed by reduction in presence of LiAlH4 or NaBH4/BF3.(C2Hs)20 to give 8-benzyl-
2,8-diazabicyclo[4.3.0]nonane of Formula IV. The compound of Formula IV is further debenzylated
using Hj/Pd to form a racemic mixture of 2,8-diazabicyclo[4.3.0]nonane of Formula I as given in
Scheme-1 below. Scheme-l

Drawbacks of this process : This patent discloses the preparation of racemic 2,8-Diazabicyclo [4.3.0]nonane and there is no resolution of the racemic mixture to form the specific isomer. Also it involves handling and use of UAIH4 for reduction, which is hazardous and economically less viable at

commercial scale.
US5770597. EP690862 and JP08505385 discloses a process for preparing (S,S)-2,8 diazabicyelo[4.3.0]nonane from pyridine dicarboxylate. The process comprises esterification of the diacid of Formula V in presence of thionyl chloride and methanol to form an ester of Formula VI which is reduced in the presence of L1AIH4 to form to a diol of Formula VII .This diol is further chlorinated, brominated or methane sulphonated to form a compound of Formula VIII and cyclised in the presence of tosylamide and sodium hydride to give a compound of Formula IX .The compound of formula IX is hydrolyzed in the presence of 48% hydrobromic acid to give compound of formula X, converted to suitable salt form of formula XI and hydrogenated to give compound of Formula I as given in Scheme- 2 below. Scheme-2

Drawbacks of this process : The process disclosed in this patent involves protection, deprotection twice, which increases the number of step and affects the overall yield of the product. Also it involves handling and use of LiAlH4 for reduction, which is hazardous and economically less viable at commercial scale.
US5480879. DE4208792. DE4208789, EP592868 and DE4234330 also discloses a process for the preparation of (S.S)-2,8-diazabicyclo[4.3.0]nonane the process of which comprises of separation of the diastereomeric salt of 8-benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV using D(-) tartaric acid followed by recrystallization to give enantiomerically pure (S,S)-8-benzyl-2,8-diazabicyclo [4.3.0]nonane of Formula XII followed by debenzylation to form (S,S)-2,8-diazabicyclo[4.3.0]nonane of Formula I as shown in Scheme-3 below. Further the compound is purified by distillation.


Drawbacks: This process comprises extra steps of purification which reduces the product yield and increases cost of the and time. Also it involves use of high vacuum, which is very difficult to achieve at the commercial scale, this adds to the cost of production.
Yet another approach described in this patent comprises of treating cis-8-benzyl-2,8-diaza bicyclo[4.3.0]nonane with L(+)-tartaric acid followed by seeding with (R,R)-8-benzyl-2,8-diazabicyclo [4.3.0]nonane L-tartarate at a temperature of 20°C and filtration. The filtrate is seeded with (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane L-tartarate until crystallization is complete. The mixture is filtered and distilled. The residue is treated with sodium hydroxide in presence of ether and the solvent is distilled off under vacuum to give compound of Formula I.
(S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D-tartarate can be obtained from mother liquor by purification with D-(-)-tartaric acid, filtered and washed with isopropanol and dimethylformamide. The product is dried and recrystallised from 88% ethanol. This can be best illustrated by Scheme 3 above
Drawbacks: It is difficult to get the pure product using this procedure, moreover pure product

cannot be obtained without seeding and or recrystallization. Extra purification results in loss of yields and will directly add to production cost..
Zhongguo Yiyao Gongye Zazhi, 35(3), 129-131; 2004 describes the process for synthesis of nonane which process comprises of the following scheme 4 below

Drawbacks: It involves handling and use of LiAlFLt for reduction, which is hazardous and economically less viable at commercial scale.
Thus there is a continuous need for preparing improved and commercially viable and safe method for the manufacture of (S,S)-2,8-diazabicyclo[4.3.0]nonane which avoids the drawbacks associated with the methods reported in the prior art more specifically handling and use of LiAlH4 for reduction, which is hazardous, unsafe and economically less viable at commercial scale and purification by distillation at 0.1 mm hg vacuum, which is less feasible at industrial scale and economically not viable.
SUMMARY OF THE INVENTION
The present invention relates to a process for manufacture of (S,S)-2,8-Diazabicyclo[4.3.0] nonane of Formula I
which comprises of:
(a) reacting pyridine dicarboxylic acid of Formula V with acetic anhydride followed by treatment
with benzyl amine to give 5H-pyrrolo[3,4-bJpyridine-5,7(6H)-dione of Formula II,
(b) 5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione is then reduced to form cis-8-Benzyl-7,9-dione-2,8-

diazabicyclo[4.3.0] nonane of Formula III in presence of 5% palladium on carbon in a suitable solvent.
(c) purification of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane of Formula III by acid base treatment,
(d) cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0] nonane is further reduced in the presence of 70% solution of Sodium Bis(2-Methoxyethoxy)Aluminum-Hydride in toluene, ,commercially known as Vitride, to form cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV in suitable solvent.
(e) cis-8-Benzyl-2,8-diazabicyclo[4.3.0Jnonane is treated with chiral resolving agents to form (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane salt of Formula XIV with >99% purity,
(t) (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane salt is further converted to its free base in the
presence of sodium hydroxide or potassium hydroxide to give (S,S)-8-benzyl-2,8-
diazabicyclo[4.3.0]nonane of Formula XII in a suitable solvent (g) (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0] nonane is debenzylated with a 5% palladium on carbon,
followed by distilling and codistilling the solvent to give (S,S)-2,8-diazabicyclo[4.3.0] nonane,
a compound of Formula I.
In a preferred embodiment of the present invention, the reduction of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane of Formula III to cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV is carried out with 70 % solution of Vitride in toluene which is an industrially viable, less hazardous, easily decomposable reducing agent as compared to the reducing agents already mentioned for this reaction in the prior-art.
The details of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description and claims.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a process for the preparation of (S,S)-2,8-Diazabicyclo [4.3.0] nonane of Formula I. The process is given below in Scheme 5


which comprises of:
(a) reacting pyridine dicarboxylic acid of Formula V with acetic anhydride followed by treatment
with benzyl amine to give 5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of Formula II,
(b) 5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione is then reduced to form cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0] nonane of Formula III in presence of 5% palladium carbon in a suitable solvent,
(c) purification of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0] nonane of Formula III by acid base treatment,
(d) cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0] nonane is further reduced in the presence of
70% solution of Sodium Bis(2-Methoxyethoxy)Aluminum-Hydride in toluene, commercially
known as Vitride, to form cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV in
suitable solvent,
(e) cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane is treated with chiral resolving agents to form
(S,S)-8-benzyI-2,8-diazabicycIo[4.3.0]nonane salt of Formula XIV with >99% purity,
(f) (S,S)-8-benzyI-2,8-diazabicyclo[4.3.0]nonane salt is further converted to its free base in the
presence of sodium hydroxide or potassium hydroxide to give (S,S)-8-benzyl-2,8-
diazabicyclo[4.3.0]nonane of Formula XII in a suitable solvent
(g) (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0] nonane is debenzylated with a 5% palladium on carbon,
followed by distilling and codistilling the solvent to give (S,S)-2,8-diazabicyclo[4.3.0] nonane,

a compound of Formula 1.
According to the process of the present invention the reaction of pyridine dicarboxylic acid of Formula V with acetic anhydride is carried out at a temperature of about 100-125°C, preferably at 110-115°C.
In a preferred embodiment the solvents used in for reduction of 5H-pyrroIo[3,4-b]pyridine-5,7(6H)-dione to form cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane with 5% palladium on carbon are selected from methanol, ethanol, propanol, more preferably methanol.
In a preferred embodiment of the present invention, the reduction of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane of Formula III to cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV is carried out with 70 % solution of Vitride in toluene which is an industrially viable, less hazardous, easily decomposable reducing agent as compared to the reducing agents already mentioned for this reaction in the prior-art.
According to the process of the present invention the chiral resolving reagents used in step (d) is selected from D(-)Tartaric acid, D-Mandelic acid, more preferably D(-)tartaric acid in suitable solvents selected from N,N-Dimethylacetamide, N,N-dimethylformamide, more preferably N,N-dimethylformamide.
According to the process of the present invention the base used to convert the salt obtained in step (d) to a free base is sodium or potassium hydroxide, more preferably sodium hydroxide in presence of a mixture of solvents selected from water, hydrocarbons and or etheral'solvents, like toluene, cyclohexane, diethyl ether, diisopropyl ether, more preferably diisopropyl ether.
According to the process of the present invention the debenzylation is carried out in solvents selected from methanol, ethanol, propanol, more preferably methanol.
Another embodiment of the present invention relates to the process for manufacture of (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D tartrate salt directly from the reaction mass and does not require any cumbersome procedure of isolating the (R,R) isomer first and then isolating the desired isomer from mother liquor.
(S,S)-2,8-Diazabicyclo[4.3.0]nonane of Formula I as obtained by the process mentioned as above has GC purity of more than 99.5 % and having less than 0.5 % content of the other isomer (R,R)-2,8-Diazabicyclo[4.3.0]nonane.
Another embodiment of the present invention relates to the process for manufacture of 1-cyclopropyl-7-[(S.S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fiuoro-8-methoxy-l,4-dihydro-4-oxo-3

quinoline carboxylic acid commercially known as Moxifloxacin hydrochloride monohydrate with HPI.C purity greater than 99.5 % and less than 0.5 % of the other isomer, using (S,S)-2,8-Diazabicyclo|4.3.0]nonane of present invention, which comprises of:
a) Reaction of cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic
acid with (S, S)-2,8-diazabicyclo[4.3.0]nonane of formula I in presence of triethylamine and
acetonitrile
b) Conversion of the crude base l-cyclopropyl-7-(2,8diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-
methoxy-4-oxo-l,4-dihydro-3-quinoline carboxylic acid hydrochloride monohydrate in the
presence of purified water and methanol hydrochloride
c) purification of 1 -cyclopropyl-7-(2,8-diazabicyclof4.3.0]nonan-8-yl)-6-fluoro-8-methoxy-4-oxo-
1.4-dihydro-3-quinoline carboxylic acid hydrochloride monohydrate by using activated carbon
in presence of 50 % aqueous methanol.

ADVANTAGES OF THIS PROCESS ;
The advantages of this invention over prior-art are :
• (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D(-)tartarate salt obtained is enantio-merically
pure, >99.5 %, and does not require any further purification,
• purification of dione is done by acid-base treatment, thus avoiding purification through
chromatographic techniques,
• use of 70 % solution of Sodium Bis(2-Methoxyethoxy)Aluminum-Hydride in toluene, which is
chemically known as Vitride as reducing agent which is cheap, less hazardous, easy to handle
and easy to decompose once the reaction gets over,
• (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane is obtained directly and does not require any
cumbersome procedure of isolating the (R,R) isomer first and then isolating the desired isomer
from mother liquor.

1 (S.S)-8-2,8-diazabicyclo[4.3.0]nonane obtained is more than 99.5 % purity by GC, other isomer less than 0.5% and does not require any purification like crystallization or distillation under vacuum The invention is further illustrated by the following non-limiting examples.
EXAMPLES
Example-1: Preparation ofSH-pvrrolof3J-blpyridine-5.7(6H)-dione.
To acetic anhydride (60 ml) was added pyridine-2,3-dicarboxylic acid (60g, 0.3592mole). The reaction mixture was heated to 110°C and maintained for 4 hours at 110°C. The reaction mixture was cooled to 80°C, the solvent was distilled off completely under vacuum below 80°C and cooled to room temperature. Methylene chloride (60 ml) was charged to the residue, stirred for 30 minutes at 40-45°C. The solvent was distilled off completely. The process was repeated. Finally, to the crude reaction mass was added methylene chloride followed by cooling the reaction mass to 0-5°C. Benzylamine (45.36g, 0.4239mole) was added to it dropwise maintaining a temperature of 0-10°C over a period of 1 hour and heated to 80-90°C for a period of 30 minutes. The reaction mixture was cooled to 70-75°C, followed by dropwise addition of acetic anhydride (60 ml). The reaction mixture was heated to 110-115°C for 3 hours, followed by cooling to 60-65°C. The acetic acid was distilled under reduced pressure followed by the addition of ethanol. The reaction mixture was cooled to 0-5°C , stirred for 1 hour, washed with ethanol and dried at 60-65°C in air oven for 5 hours. Dry weight: 72.48 g. Example-2: Preparation of8-Benzvl-7,9-dione-2,8-diazabicyclo[4.30fnonane.
5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione (72.48g, 0.3045mole) in methanol (217.44ml) was charged with 5% Pd/C (7.24 g) under nitrogen atmosphere in an autoclave. The reaction vessel was evacuated followed by application of Hydrogen gas at a pressure of 4.0-4.5 kg/cm'. The reaction mixture was heated at a temperature of 55-60°C for a period of 7 hours. The reaction mixture was filtered and then washed with methanol. The solvent was distilled off completely under vacuum below 45°C. Example-3: Purification of8-Benzvl-7,9-dione-2,8-diazabicyclo/4.30f nonane.
Isopropyl alcohol (182ml) was added to the crude material obtained after distillation from example-2, the reaction mixture was heated to 60°C for dissolution The pH of the reaction mixture was adjusted to 2.0 with IPA.HC1 (82.14ml) below 20°C followed by stirring for a period of 30 minutes.

The solid seperated was filtered and then washed with chilled isopropanol, followed by hexane wash.To this HC1 salt was added toluene (145ml) is added and cooled to 15°C followed by the drop wise addition of triethylamine (28.9ml. 0.3045mole) to adjust the pH to 9 to 10. The reaction mixture was stirred for 30 minutes at 20°C. salts are removed by filtration. The filtrate is distilled under reduced pressure below 60°C to get the desired product. Constant weight- 62.45g. To the crude was added toluene at 60°C to proceed for the next step. Example-4: Preparation ofCis-8-benzvl-2.8-diazabicyclol4.3.0l nonane.
8-Benzyl-7,9-dione-2,8-diazabicyclo[4.30]nonane (62.45g,0.2559mole) as obtained from the Example 2 above was dissolved in toluene (125mL) at 50°C, the reaction mixture was cooled to 0-5°C followed by the addition of vitride (332.4g, 1.4518mole). To this reaction mixture was further added with the toluene solution for 2 hours. The reaction mixture was stirred for 30 minutes and the temperature was raised to 27-30°C and maintained for 1 hour. The reaction mixture was further heated to 62-67T for 4 hours, cooled to room temperature and then to 0-5°C followed by the addition of 20% sodium hydroxide solution. The reaction mixture was again heated to 55°C, stirred for 30 minutes and the toluene layer was separated, washed with saturated sodium chloride solution and distilled off under vacuum below 60 ° C. Constant weight-52.61 gm Example-5 : Preparation of(S,S)-8-benzvl-2,8-diazabicyclo/4.3.0l nonane D(-) tartrate salt.
To cis-8-benzyl-2,8-diazabicyclo[4.3.0]nonane (52.6lg, 0.2435mole) in dimethylformamide (109.6ml) was added D(-) tartaric acid (54.8lg, 0.3654mole) and heated to 80°C for 2 hours at 80°C. The reaction mass was cooled slowly to 25-30°C and stirred for 30 minutes and further cooled to 0-5°C for 1 hour. The reaction mixture was filtered and the crystals were washed with dimethylformamide and isopropyl alcohol under nitrogen atmosphere, dried for 15 minutes under nitrogen atmosphere, to obtain the desired product. Dry weight: 36.44g. Exanwle-6: Preparation of (S,S)-8-benzvI -2.8-diazabicyclol4.3.01 nonane.
To (S.S)-8-benzyl-2,8-diazabicyclo[4.3.0|nonane D(-) tartarate salt (36.44g, 0.0995mole) in demineralized water (36.44ml) was added diisopropyl ether (36.44ml) and cooled to 20-25°C. To the reaction mixture was slowly added 45 % NaOH (36.44ml) at 20-25°C and stirred for 30 minutes. The temperature was slowly raised to 35°C and stirred for 30 minutes, the layers were separated and organic layer was distilled under reduced pressure below 40-45°C. The sample was preserved under nitrogen atmosphere. Dry weight-17.78 gm

Examole-7: Preparation of(S,S)-2,8-diazabicvclof4.3.0/ nonane.
(S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane (17.78g, 0.0823 mole) was taken in methanol (53.34ml) and reduced in presence of 5% Pd/C (3.9g) under nitrogen atmosphere. The reaction mass was heated to 55°C for 4 hrs , cooled to 25°C, filtered and washed with methanol (9.0 ml). The solvent was distilled off. Methanol is again added and codistilled the solvent under reduced pressure at 50-55°C to get the desired product. Constant weight: 10.3 gm. [a]n~2: -2°, ee>99.5% by gas chromatography, moisture content: 0.3%
Example-8: Preparation of l-cvclopropyl-7-(2.8diazabicvclo l4.3.01non-8-vl)-6-fluoro-8-methoxv-4-oxo-l,4-dihvdro-3-auinoline carboxvlic acid.
l-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-l,4-dihydro-3-quinolinecarboxylic acid (lOOg, 0.338 mole) and triethylamine were taken in mixture of acetonitrile (300 ml) and dimethylformamide (80 ml) . To it was added (S,S)-2,8-diazabicyclo [4.3.0] nonane (47g, 0.373 mole) and refluxed at 72-78°C for 10 hours at reflux. The reaction mixture was cooled to room temperature, and further to 0-5°C maintained for 1 hr, filtered and washed with acetonitrile (50 ml) to get the desired product.
Dry wt: 89.7g, Yield: 66%.
Example-9: Preparation of l-cvclopropyl-7-(2,8diazabicvclo f4.3.0Inon-8-yl)-6-fluoro-8-methoxv-4-oxo-1.4-dihvdro-3-auinoline carboxvlic acid hydrochloridemonohvdrate.
The compound obtained from the example 6(85g) was taken in methanol (250 ml) and purified water (150 ml) followed by the addition of hydrochloric acid (17.14 g) and EDTA disodium salt (57 mg) the contents was heated to 35-38°C and maintained for 1 hour ,cooled to 0-5°C for 1 hour. The product was filtered washed with methanol treated with activated carbon (5.0 g) to get the desired product. Dry wt: 53.0g, Yield: 54.84%
Although the invention has been disclosed in connection with certain preferred embodiments, it is not limited thereto. Rather, the invention includes all embodiments which may fail within the scope of the following claims.

We claim:
1. A process for the preparation of (S,S)-2,8-diazabicyclo[4.3.0]nonane of Formula I, having purity of more than 99.5 % and less than 0.5 % content of the other isomer and moisture content less than 0.5%. comprises of:
a) reacting pyridine dicarboxylic acid of Formula V with acetic anhydride followed by treatment with benzyl amine to give 5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione of Formula II,
b) 5H-pvrrolo[3.4-b]pyridine-5,7(6H)-dione is then reduced to form cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane of Formula III in presence of 5% palladium carbon in a suitable solvent,
c) purification of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane of Formula III by acid base treatment,
d) cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane is further reduced in the presence of 70% solution of Sodium Bis(2-Methoxyethoxy)Aluminurn-Hydride in toluene, commercially known as Vitride, to form cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane of Formula IV in suitable solvent.
e) cis-8-Benzyl-2.8-diazabicyclo[4.3.0]nonane is treated with chiral resolving agents to form (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D tartrate salt of Formula XIV with >99.5% purity.
0 (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D tartrate salt salt is further converted to its free
base in the presence of sodium hydroxide or potassium hydroxide to give (S,S)-8-benzyl-2,8-
diazabicyclo[4.3.0]nonane of Formula XII in a suitable solvent g) (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane is debenzylated with a 5% palladium on
carbon,distilling and codistilling the solvent to give (S,S)-2,8-diazabicyclo[4.3.0]nonane, a
compound of Formula I.
2. The process as in Claim 1 above, wherein the conversion as in Step (a) is done neat,
3. The process as in claim 1 above, wherein conversion of pyridine dicarboxylic acid to 6-benzyl-5H-pyrrolo[3,4-b] pyridine-5,7(6H)-dione as in Step (a) is carried out at 110-115°C.
4. The process as in claim 1, wherein solvents used in step (b) for reduction of 5H-pyrrolo[3,4-bjpyridine-5.7(6H)-dione to cis-8-Benzyl-7.9-dione-2,8-diazabicyclo[4.30]nonane in presence of 5% pd on carbon are selected from methanol, ethanol, propanol, preferably methanol.

5. The process as claimed in claim 1. wherein the purification of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane as in Step (c) is done by acid-base treatment.
6. The process as claimed in claim 1, wherein the reduction of cis-8-Benzyl-7,9-dione-2,8-diazabicyclo[4.3.0]nonane to cis-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane is done in the presence of safe and an improved reducing agent, commercially known as Vitride, which is a 70% solution of Sodium Bis(2-Methoxyethoxy)Aluminum-Hydride in toluene.
7. The process as claimed in claim 1, wherein the chiral resolving reagents as used in Step (e) is selected from D(-)Tartaric acid, D-Mandelic acid, more preferably D(-)tartaric acid in suitable solvents selected from N,N-Dimethylacetamide, N,N-dimethylformamide, more preferably N,N-dimeth\iformamide.
8. The (S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D tartrate salt obtained in step (e) is isolated directly from the reaction mass is more than 99.5% purity and does not require further purification
9. The process as claimed in claim 1, wherein the conversion as in Step (f) of (S,S)-8-benzyl-2,8-
diazabicyclo[4.3.0] nonane D tartrate salt into (S,S)- 2,8-diazabicyclo[4.3.0] nonane is carried
out in a mixture of solvents selected from water and any of the hydrocarbons or etheral solvents
such as toluene, cyclohexane, diethyl ether, diisopropyl ether, preferably diisopropyl ether.
10. The process for preparation of l-cyclopropyl-7-[(S,S)-2.8-diazabicyclo[4.3.0]non-8-yl]-6-
fluoro-8-methoxy-l,4-dihydro-4-oxo-3 quinoline carboxylic acid commercially known as
Moxitloxacin hydrochloride monohydrate with HPLC purity greater than 99.5 % and less than
0.5 % of the other isomer, using (S,S)-2,8-Diazabicyclo[4.3.0]nonane of present invention,
which comprises of:
a) Reaction of cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid with (S,S)-2,8-diazabicyclo[4.3.0Jnonane of formula I, as prepared in Claim 1 above, in presence of triethylamine and acetonitrile
b) conversion of the crude base to l-cyclopropyl-7-(2,8-diazabicyclo [4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-l,4-dihydro-3-quinoline carboxylic acid hydrochloride monohydrate in the presence of purified water and methanol hydrochloride
c) purification of l-cyclopropyl-7-(2,8diazabicyclo [4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-l,4-dihydro-3-quinoline carboxylic acid hydrochloride monohydrate by using activated carbon in presence of 50% aqueous methanol.