DESC:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:

“PROCESS FOR THE PREPARATION OF MOXIFLOXACIN”

2. APPLICANT:

(a) NAME: INDOCO REMEDIES LIMITED

(b)NATIONALITY: Indian Company incorporated under the
Companies Act, 1956

(c) ADDRESS: Indoco House, 166 C.S.T. Road, Santacruz (East),
Mumbai – 400 098, Maharashtra, India.

3.PREAMBLE TO THE DESCRIPTION:

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 an improved process for the preparation of moxifloxacin hydrochloride of formula I.

Formula I

BACKGROUND AND PRIOR ART:
Moxifloxacin hydrochloride is a synthetic broad spectrum antibacterial agent chemically known as 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride.

Moxifloxacin hydrochloride belongs to fluoroquinolone class of anti-infective compounds and has been shown to be clinically active against most strains of microorganisms such as aerobic gram-positive microorganisms including Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, aerobic gram-negative microorganisms including Haemophilus Influenzae, Haemophilus parainfluenza and Klebsiella pneumoniae.

US patent 4,990,517 disclosed for the first time preparation of moxifloxacin hydrochloride involving the condensation of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid or its esters with (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of a base in an organic solvent and conversion of resulting moxifloxacin base into its pharmaceutically acceptable salts.

The above process suffers from major drawback as it leads to the formation of desired moxifloxacin along with its potential isomer namely (4aS-cis)-1-cyclopropyl-6-(2,8-diazabicyclo[4.3.0]non-8-yl)-7-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid as a major impurity. As the impurity and moxifloxacin are positional isomers, they are difficult to separate and requires chromatographic purification which is difficult to implement on industrial scale and results in low yield of the product moxifloxacin.

PCT publication WO2005/012285 A1 discloses the process for the preparation of moxifloxacin hydrochloride by the condensation of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(acyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0] nonane in the presence of base selected from triethylamine, diisopropylethylamine, DBU in polar organic solvents selected from acetonitrile, dimethylsulfoxide and dimethylformamide to give (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline- carboxylic acid-O3,O4-bis(acyloxy-O)borate. The above formed intermediate is then treated with hydrochloric acid in short chain alcohol to form moxifloxacin hydrochloride pseudo hydrate. The moxifloxacin hydrochloride pseudo hydrate upon mixing with hydrochloric acid in presence of ethanol gives moxifloxacin hydrochloride monohydrate.

The drawback in the above process involves the isolation of intermediate, synthesis of moxifloxacin hydrochloride pseudohydrate and then its conversion to its monohydrate thereby increasing the number of steps in the manufacturing process which leads to lowering of yields of the final compound.

US patent 5,849,752 discloses monohydrate of moxifloxacin hydrochloride (CDCH) and its preparation by treating the anhydrous crystalline form of moxifloxacin hydrochloride with ethanol-water mixtures at raised temperature. The crystals which have precipitated out are dried at room temperature/ambient humidity to get Moxifloxacin hydrochloride monohydrate.

PCT publication WO 2008/059223 discloses the process for the preparation of moxifloxacin hydrochloride by reacting propionic anhydride and boric acid with ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolonecarboxylate to obtain 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(propionyloxy-O) borate, then condensation of the above borate complex with (S,S)-2,8-diazabicyclo[4.3.0]nonane in an organic solvent such as acetonitrile or n-butanol to obtain the intermediate (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4-bis(propyloxy-O)borate which is hydrolyzed using hydrochloric acid in methanol and distilled off to give moxifloxacin hydrochloride. Moxifloxacin hydrochloride is then purified using base acid treatment, the purification process involves the treatment of moxifloxacin hydrochloride with a base to form moxifloxacin free base which is then converted to moxifloxacin hydrochloride by acidifying the reaction mixture.

The drawback of the above invention is the isolation of moxifloxacin hydrochloride by distillation of the reaction mixture which may lead to product decomposition and moxifloxacin hydrochloride thus prepared requires further purification with base acid treatment which adds extra steps to the process.

Indian patent application 810/MUM/2009 discloses a process for the preparation of moxifloxacin or its acid addition salt by reacting borate complex or ester of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid with (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of base and chlorinated solvent selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixture thereof.

The drawback of the invention lies in the use of chlorinated solvent to isolate the pure compound which is toxic and ICH guidelines restricts the use of the chlorinated solvents in the penultimate stage or final stage of the preparation of API & intermediates.

Indian patent application 518/DEL/2010 discloses the process for the preparation of moxifloxacin hydrochloride, wherein the borate complex of the compound 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid is prepared in presence of Lewis acid catalyst selected from zinc chloride, aluminium chloride and ferrous chloride. The borate complex is condensed with the compound (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of base and solvent, water or water immiscible organic solvent to get the compound (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinolinecarboxylic acid-O3,O4-bis(propyloxy-O)borate which on reaction with hydrochloric acid results in moxifloxacin hydrochloride.
The above invention uses the Lewis acid to prepare the borate complex of the compound 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid which evolves lot of acidic fumes during the process as well as on work up and thus pollutes the environment and therefore needs precaution and scavengers to trap the fumes.

Therefore there is a need in the art to develop an improved process to overcome disadvantages of the prior art, which involve easy isolation of intermediate as well as product, avoid the need of base acid treatment and is commercially viable.

In order to develop a rigid and efficient process for industrial synthesis of moxifloxacin hydrochloride, the present invention provides an improved process for the preparation of moxifloxacin hydrochloride, which is economically viable, industrially advantageous as well as reproducible on industrial scale.

OBJECT OF THE INVENTION:
It is an object of the present invention to provide an improved and industrially advantageous process for the preparation of moxifloxacin hydrochloride of formula I.

Another object of the present invention is to provide a process for the preparation of moxifloxacin hydrochloride through a novel intermediate compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate of formula IV;

Formula IV.

A further object of the present invention is to provide a process for the preparation of moxifloxacin hydrochloride through a novel intermediate compound (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate of formula V;

Formula V.

SUMMARY OF THE INVENTION:
Accordingly the present invention provides an improved process for the preparation of moxifloxacin hydrochloride of formula I;

Formula I
comprising the steps of;
i. reacting the compound ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate of formula II;

Formula II
with butyric anhydride in presence of boric acid and an organic solvent to get the compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4-bis(butyroxy-O)borate of formula IV;

Formula IV

ii. condensing the compound of formula IV with (S,S)-2,8-diazabicyclo[4.3.0]nonane of formula III in presence of a base and solvent to get an intermediate compound (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate of formula V,

Formula V
which on insitu hydrolysis in presence of hydrochloric acid to get moxifloxacin hydrochloride of formula I.

In an aspect, the process according to the present invention provides a novel intermediate compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4-bis(butyroxy-O)borate of formula IV;

Formula IV.

In another aspect, the process according to the present invention provides a novel intermediate compound (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate of formula V,

Formula V.

DETAIL DESCRIPTION OF THE INVENTION:
The present invention provides an improved and industrially advantageous process for the preparation of moxifloxacin hydrochloride of formula I.

Formula I
According to one embodiment, the present invention provides a process for the preparation of the moxifloxacin hydrochloride of formula I starting from compound of formula II. The process involves the reaction of compound of formula II with boric acid and butyric anhydride and optionally in presence of an organic solvent to form compound of formula IV which is then converted to moxifloxacin hydrochloride through borate complex of formula V. Since, the butyric anhydride can also acts as a solvent, the reaction goes smoothly without the use of any additional solvent.

Specifically, the process involves the preparation of the compound of formula IV by reacting the compound of formula II with boric acid and butyric anhydride in presence of an optional organic solvent at temperature in the range of 30°C to 120°C to form the borate complex. The preferred temperature for the preparation of borate complex is in the range of 80°C to 110°C and the most preferred temperature range is 105°C to 110°C. Similarly, the reaction of the compound of formula II with boric acid may also be conducted with any other anhydride selected from the group consisting of isobutyric anhydride, valeric anhydride, isovaleric anhydride, hexanoic anhydride, trichloroacetic anhydride and heptafluorobutyric anhydride. Accordingly, the solvent for the reaction may be selected from the group consisting of butyric anhydride, isobutyric anhydride, valeric anhydride, isovaleric anhydride, hexanoic anhydride, trichloroacetic anhydride and heptafluorobutyric anhydride, diethylene glycol, N,N-dimethylformamide, dimethyl sulfoxide, diglyme and hexamethylphosphoramide or combinations thereof.

The reaction of boric acid and the butyric anhydride is carried out in presence of the solvent initially at temperature of 30°C to 120°C. After complete addition of boric acid the reaction mixture is heated to 105°C to 110°C for 2 to 4 hours. The reaction mass is then cooled to 70°C and the compound ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate of formula II is added to the reaction mixture and maintained at temperature in the range of 70°C to 130°C. The anhydride used for the reaction also acts as solvent for the reaction. The preferred temperature for the reaction is in the range of 95°C – 105°C. The reaction completion can be monitored by suitable chromatographic techniques such as high pressure liquid chromatography (HPLC), thin layer chromatography (TLC) and the like, till the disappearance of the starting compound. After the completion of the reaction the reaction mass is cooled to 25°C to 35°C and charged cyclohexane to the reaction mass for isolation of the product. The reaction mixture is stirred at 20°C to 30° C for 15 minutes and subsequently cooled to 15°C . The solid separated was filtered. The wet mass is slurried in water at 15°C to 25°C filtered and dried under vacuum to get the borate complex of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate of formula IV.

The compound of formula IV is then condensed with (S,S)-2,8-diazabicyclo[4.3.0]nonane of formula III in the presence of base and solvent to get the borate complex of formula V, which forms the inventive feature of the invention. Thus the invention encompasses the novel intermediate compounds of formula IV and V, which forms part of the invention.
The compound of formula V may optionally be isolated, however, it is preferred to convert the formula V compound insitu into moxifloxacin hydrochloride of formula I so as to eliminate multiple process steps.

Accordingly as per the present invention the synthesis of borate complex of formula V involves the reaction of the compound of formula IV with (S,S)-2,8-diazabicyclo[4.3.0]nonane of formula III in the presence of base and solvent. Base employed for the reaction can be inorganic or organic base. Inorganic base can be selected from alkali or alkaline metal hydroxides, carbonates, bicarbonates thereof such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide and the like. Organic base can be selected from substituted amines such as triethylamine, diisopropylethylamine, diazabicyclo[5.4.0]undec-7-ene (DBU) and the like or combination thereof. The preferred base used for the reaction is triethyl amine. The solvent used for the reaction is selected from the group consisting of acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, diisopropyl ether, ethyl acetate, toluene, cyclohexane and water either single or mixture thereof. The preferred solvent used for the reaction is acetonitrile. The reaction can be carried out at a temperature of about 20°C to 80°C for 1 to 8 hours. The preferred temperature for the reaction is in the range of 55°C to 65°C. The time of reaction is about 2 to 4 hours. The reaction completion can be monitored by suitable chromatographic techniques such as high pressure liquid chromatography (HPLC), thin layer chromatography (TLC) and the like. Usually the reaction undergoes completion in 3 hours to give the borate complex of formula V. The borate complex of formula V can be optionally isolated from the reaction mixture by using suitable techniques known in the art.

In another embodiment of the present invention, the borate complex of compound of formula V formed according to the present invention is not isolated, however hydrolysed insitu using hydrochloric acid to yield moxifloxacin hydrochloride of formula I. After completion the reaction mixture was cooled to 40°C and charged water and stirred. To this solution, charged concentrated hydrochloric acid while maintaining the temperature in the range of 25°C to 35°C and stirred for 30 minutes at 30°C to 35°C. Cooled the reaction mass further to 0°C – 5°C and filtered the solid separated out, washed with chilled acetonitrile and dried the product under reduced pressure to get moxifloxacin hydrochloride of formula I.

The advantagelies in proceeding with the reaction mixture as such for the further formation of moxifloxacin hydrochloride without isolation of borate complex of formula V is to achieve simultaneous hydrolysis of the borate complex with the formation of salt of the compound of formula I thereby avoiding the step of hydrolysis and salt formation separately.
Optionally, if required, the compound Moxifloxacin hydrochloride of Formula I can be further purified by applying the suitable purification method available in prior art.

The reaction sequence of the present invention can be represented as follows;

The process according to the present invention provides a novel intermediate compound of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4-bis(butyroxy-O)borate of formula IV;

Formula IV.

Also disclosed is a novel intermediate compound (4aS-cis)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline- carboxylic acid-O3,O4-bis(butyroxy-O)borate of formula V, which forms part of an embodiment.

Formula V

The present invention is further illustrated in detail with reference to the following examples. It is desired that the example be considered in all respect as illustrative and are not intended to limit the scope of the present invention.

Examples:

Example 1: Preparation of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate:

In a dry flask charged butyric anhydride (50 gm) at 25 - 30°C. Raised the temperature of the reaction to 80 - 90°C and slowly added boric acid (6 gm), stirred for few minutes. Raised the temperature of the reaction mixture to 170°C and maintained at 170 - 180°C for 2 - 3 hours. The reaction mixture cooled to 70°C and charged ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylate (20 gm) and maintained the reaction mixture at 100 - 110°C for 4 - 5 hours. After completion of the reaction, cooled the reaction mixture slowly to 0°C. Charged chilled water (200 ml) and stirred for 2 - 3 hours. Filtered the solid mass and washed with chilled water (100 ml) and dried to get 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid -O3,O4-bis(butyroxy-O)borate.
Dry weight= 29.0 gm.

Example 2: Preparation of Moxifloxacin Hydrochloride:

In a dry flask charged acetonitrile (150 ml), triethylamine (15.5 gm), stirred and charged 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate (29 gm) and (S,S)-2,8-diazabicyclo[4.3.0]nonane (10 gm). Raised the temperature of the reaction mass to reflux and maintained for 5 - 6 hours. After completion of the reaction cooled the reaction mass to 40°C and distilled out solvent under reduced pressure maintaining temperature at 40 - 45°C. To the residual mass charged diisopropyl ether (150 ml) and stirred for 1 hour. Distilled out solvent under reduced pressure and charged methanol (150 ml), stirred further for 1 hour. Charged concentrated hydrochloric acid to the reaction mixture and cooled to 0°C and maintained for 2 hours at 0 - 5°C. Filtered the solid mass and washed with chilled methanol and dried the product under vacuum to get moxifloxacin hydrochloride.
Dry weight= 20.0 gm.

Example 3: Preparation of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid-O3,O4-bis(butyroxy-O)borate:

In a dry flask charged butyric anhydride (50 gm) at 25 - 30°C. Raised the temperature of the reaction to 80 - 90°C and slowly added boric acid (6 gm), stirred for few minutes. Raised the temperature of the reaction mixture to 105°C - 110°C and maintained for 3 hours at 105°C - 110°C. The reaction mixture cooled to 70°C and charged ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylate (20 gm) and maintained the reaction mixture at 95 - 100°C for 4 - 5 hours. After completion of the reaction, the reaction mass was cooled to 30-35°C and Cyclohexane (80 ml) was added. The mixture was stirred at this temperature for 30 minutes, cooled to 15°C and filtered. The wet cake was then stirred in (120ml) water at room temperature and filtered at 15°C -20°C to get 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline- carboxylic acid -O3,O4-bis(butyroxy-O)borate.
Dry weight= 29.0 gm.

Example 4: Preparation of Moxifloxacin Hydrochloride:

In a dry flask charged acetonitrile (150 ml), triethylamine (15.5 gm), stirred and charged 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid -O3,O4-bis(butyroxy-O)borate (29 gm) and (S,S)-2,8-diazabicyclo[4.3.0]nonane (10 gm). Raised the temperature of the reaction mass to 55-60°C and maintained for 3 hours. After completion of the reaction cooled the reaction mass to 40°C and added water (15ml).Adjusted the pH 1-2 using conc. hydrochloric acid. Maintained the reaction mass at 30°C - 35 °C for 30 minutes; cooled the reaction mass to 0°C - 5°C and filtered. The filtered wet cake was washed with chilled acetonitrile and dried the product under vacuum to get Moxifloxacin hydrochloride.
Dry weight= 20.0 gm. ,CLAIMS:We claim:

1. A process for the preparation of moxifloxacin hydrochloride of Formula I;

Formula I
comprising the steps of;

iii. reacting the compound ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate of Formula II;

Formula II
with butyric anhydride in presence of boric acid and an organic solvent at raised temperature to obtain the compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid -O3,O4-bis(butyroxy-O) borate of Formula IV;

Formula IV
iv. condensing the compound of Formula IV with (S,S) -2.8 Diazabicyclo [4.3.0] nonane in presence of a base and solvent to obtain an intermediate compound (4aS-Cis)-1-Cyclopropyl-7-(2,8 diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic aid-O3,O4-bis(butyroxy-O)borate of Formula V,

Formula V
which on insitu hydrolysis in presence of hydrochloric acid results in moxifloxacin hydrochloride of Formula I.

2. The process as claimed in claim 1, wherein the organic solvent used for the reaction in step (i) is selected from the group consisting of butyric anhydride, isobutyric anhydride, valeric anhydride, isovaleric anhydride, hexanoic anhydride, trichloroacetic anhydride and heptafluorobutyric anhydride, diethylene glycol, N,N-dimethylformamide, dimethyl sulfoxide, diglyme and hexamethylphosphoramide or combinations thereof.

3. The process as claimed in claim 1 and 2, wherein the solvent used for the reaction in step (i) is butyric anhydride.

4. The process as claimed in claim 1, wherein the reaction in step (i) is performed in presence of boric acid and an organic solvent at temperature in the range of 70°C to 130°C.

5. The process as claimed in claim 4, wherein the temperature of the reaction in step (i) is maintained in the range of 95°C to 105°C.
6. The process as claimed in claim 1, wherein the base used for the reaction in step (ii) is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, diisopropylethylamine, diazabicyclo[5.4.0]undec-7-ene (DBU) or combinations thereof.

7. The process as claimed in claim 6, wherein the base used for the reaction in claim 1 step (ii) is triethylamine.

8. The process as claimed in claim 1, wherein the solvent used for the reaction in step (ii) is selected from the group consisting of acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, diisopropyl ether, ethyl acetate, toluene, cyclohexane and water either alone or in combinations thereof.

9. The process as claimed in claim 8, wherein the solvent used for the reaction in claim 1 step (ii) is acetonitrile.

10. The compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid -O3,O4-bis(butyroxy-O) borate of Formula IV;

Formula IV.

11. The compound (4aS-Cis)-1-Cyclopropyl-7-(2,8 diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic aid-O3,O4-bis(butyroxy-O)borate of Formula V;

Formula V.