Field of the invention:

The present invention relates to novel and improved processes for the preparation of anticoagulant drug i.e, 5-cWoro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-moipholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide represented by the structural formula-1. Formula-1 The present invention also relates to novel intermediates, which are useful in the preparation of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l ,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide.

Background of the invention:

US7157456 (hereafter referred to as "456") first disclosed the process for the preparation of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide which is commonly known as Rivaroxaban, an orally effective, direct inhibitor of the serine protease factor Xa which performs an essential function in regulating the coagulation of blood. US Patent No. 7157456 describes a method for preparing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide compound of formula-1, by reacting 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione with 4-(4-aminophenyl)-3-morpholinone to give 2-((2R)-2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)-phenyl]amino}propyl)-lH-isoindole-l,3(2H)dinoe Subsequently, 2-((2R)-2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)-phenyl]amino} propyl)-lH-isoindole-l,3(2H)dione reacts with N,N-Carbonyldiimidazole and 4-Dimethylamino pyridine to give 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}-methyl)-lH-isoindole-l,3(2H)dione.

Elimination of the phthalimide protective group from 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}-methyl)-lH-isoindole-l ,3(2H)dione affords 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholine-3-one which finally reacted with 5-chlorothiophene-2-carbonyl chloride to give 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide. However, the process disclosed in "456" exhibits various disadvantages including tedious chromatographic purifications which are cost-effective, not amenable for commercial synthesis on industrial scale and thereby making the process commercially unfeasible. WO2004060887 also disclosed the process for the preparation of Rivaroxaban which involves the usage of toxic reagents and solvents, hence not recommended for commercial process. Therefore, there is an obvious need for the development of a cost-effective and industrially viable process for the preparation of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide and that do not involve the chromatographic purification techniques.

Brief description of the invention:

The first aspect of the present invention relates to novel acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of general formula-3. The second aspect of the present invention is to provide a process for the preparation of novel acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one compound of general formula-3 The third aspect of the present invention is to provide a novel process for the preparation of (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)thiophene-2- carboxamide compound of formula-11. The fourth aspect of the present invention is to provide a novel process for the preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2. The fifth aspect of the present invention relates to novel intermediate compounds for the synthesis of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide compound of formula-1.

Brief description of drawings:

Figure 1: Illustrates the PXRD pattern of compound of formula-3a.

Figure 2: Illustrates the DSC thermogram of compound of formula-3a.

Figure 3: Illustrates the PXRD pattern of compound of formula-3b.

Figure 4: Illustrates the DSC thermogram of compound of formula-3b.

Figure 5: Illustrates the PXRD pattern of compound of formula-3c.

Figure 6: Illustrates the PXRD pattern of compound of formula-3d.

Figure 7: Illustrates the PXRD pattern of compound of formula-3e.

Detailed description of the invention:

As used herein, the term "suitable solvents" used in the present invention is selected from, but are not limited to "alcoholic solvents" such as methanol, ethanol, isopropyl alcohol, n-propanol, butanol and the like; "ester solvents" such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like, "ether solvents" such as tetrahydrofuran, diethylether, methyltert-butyl ether, dioxane and the like; "hydrocarbon solvents" such as toluene, xylene, cyclohexane, hexane, heptane, n-pentane, petroleum ether and the like; "chloro solvents" such as dichloromethane, ethylene dichloride, carbon tetra chloride, chloroform and the like; "polar aprotic solvents" such as dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like; "nitrile solvents" such as acetonitrile and the like; "ketone solvents" such as acetone, methyl isobutyl ketone and the like; "polar solvent" such as water.

As used herein, the term suitable "acid" is selected from "organic acids" such as oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphorsulfoic acid, ethane sulfonic acid, gluconic acid, glutamic acid, methanesulfonic acid, mucic acid, pamoic acid, pantothenic acid, paratoluene sulfonic acid and "inorganic acids" such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid and phosphoric acid. As used herein, the term "base" is selected from inorganic bases like alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide; alkali metal alkoxides such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide; alkali metal carbonates like sodium carbonate, potassium carbonate; alkali metal bicarbonates like sodium bicarbonate and potassium bicarbonate and organic bases like triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, dimethyl formamide, pyridine, tributyl amine, 4- dimethylaminopyridine, N-methyl morpholine and the like.

As used herein, the term "coupling agent" is selected from dicyclohexyl carbodiimide (DCC), diisopropylcarbodiimide (DIC), ethyl-(N',N'-dimethylamino) propylcarbodiimide hydrochloride (EDC), N, N-carbonyldiimidazole (CDI), DABAL-Me3. As used herein, the term "alkyl" refers to alkyl group having 1 to 4 carbon atoms. Examples of Ci to C4 alkyl groups include, without limitation, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl. As used herein the term "deprotecting agent" is selected from hydrazine hydrate, sodiumborohydride/acetic acid, methylamine, ethylamine, methanolamine, ethanolamine, 1,2-diaminoethane As used herein the term "cyclizing agent" is selected from N,N-carbonyl diimidazole/NMP, N,N-Carbonyldiimidazole/DMAP. As used herein the term "chlorinating agent" is selected from pivaloyl chloride, thionyl chloride, phosphorus oxychloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride and the like.

The first aspect of the present invention relates to novel acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compounds of general formula-3 is represented by Formula-3 wherein, the acid is selected from inorganic acids such as hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid and phosphoric acid; and organic acids such as oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphorsulfoic acid, ethane sulfonic acid, gluconic acid, glutaric acid, glutamic acid, methanesulfonic acid, mucic acid, pamoic acid, pantothenic acid, para toluene sulfonic acid and the like. Further the present invention provides the acid addition salt compounds of formula-3 as a crystalline solid. The preferred embodiment of present invention provides acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-3 as a crystalline solid.

The crystalline acid addition salt compound of general formula-3 comprising;

a) The crystalline oxalic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3a is characterized by,

i) its PXRD pattern substantially in accordance with figure-1,

ii) its powder X-Ray diffractogram having peaks at 5.14, 15.5, 16.9, 17.6, 18.1, 19.6, 19.9,
20.3,20.5,23.4,25.6,26.8,28.7,29.0 and 31.6±0.2 degrees of two-theta, and iii) its DSC thermogram substantially in accordance with figure-2;

b) The crystalline maleic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3b is characterized by,

i) its PXRD pattern substantially in accordance with figure-3,

ii) its powder X-Ray diffractogram having peaks at 4.8, 14.5, 18.37, 18.8, 20.5, 21.1, 21.9, 24.5,24.9,25.529.5 and 34.6±0.2 degrees of two-theta, and iii) its DSC thermogram substantially in accordance with figure-4;

c) The crystalline succinic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3 c is characterized by,

i) its PXRD pattern substantially in accordance with figure-5,

ii) its powder X-Ray diffractogram having peaks at 5.8, 11.7, 16.4, 17.6, 19.9, 21.6, 22.0, 23.6,24.6, 26.1,28.7 and 31.5±0.2 degrees of two-theta;

d) The crystalline fumaric acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3d is characterized by,

i) its PXRD pattern substantially in accordance with figure-6,

ii) its powder X-Ray diffractogram having peaks at 2.6, 3.9, 7.9, 14.4, 16.2,20.6, 24.0,24.7, 28.6 and 29.3±0.2 degrees of two-theta;

e) The crystalline malic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3d is characterized by,

i) its PXRD pattern substantially in accordance with figure-7,

ii) its powder X-Ray diffractogram having peaks at 12.8, 14.5, 14.9, 15.3, 17.2, 17.5, 19.8, 21.6, 23.0,24.5 and 26.0±0.2 degrees of two-theta; The acid addition salt compounds of general formula-3 of the present invention are used for the preparation of highly pure 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2.

Further the compounds of general formula-3 are converted to highly pure 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2 by treating with a suitable base in a suitable solvent. The suitable base and solvents are same as defined above. The second aspect of the present invention provides a process for the preparation of acid addition salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of general formula-3, comprising of:

a) Dissolving the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one compound of formula-2 in a suitable first organic solvent,

b) dissolving a suitable organic acid in a suitable second organic solvent and adding the resulting solution to the reaction mixture obtained in step-(a),

c) stirring the reaction mixture,

d) filtering the precipitated solid.

Wherein, in step-(b) the suitable acid used is selected from "organic acids" such as oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphorsulfoic acid, ethane sulfonic acid, gluconic acid, glutamic acid, methane sulfonic acid, mucic acid, pamoic acid, pantothenic acid, para toluene sulfonic acid; and "inorganic acids" such as hydrochloric acid, hydro bromic acid, hydroiodic acid, nitric acid, sulfuric acid and phosphoric acid; in step-(a) the suitable first organic solvent used is selected from chloro solvents; in step-(b) the suitable second organic solvent used is selected from alcoholic solvents. The third aspect of the present invention provides a novel process for the preparation of (S)-5 -chloro-N-((3 -(4-fluorophenyl)-2-oxo-1,3 -oxazolidin-5 -yl)methyl)thiophene-2-carboxamide compound of formula-11, a useful intermediate in the synthesis of compound of formula-I, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in presence or absence of a suitable base in a suitable solvent provides (S)-2-(3-(4-fluoro phenylamino)-2-hydroxypropyl)isoindoline-1,3-dione compound of formula-7, Formula-7 b) reacting the compound of formula-7 with a suitable cyclizing agent in presence of a suitable catalyst in a suitable solvent provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8, Formula-8 c) reacting the compound of formula-8 with a suitable deprotecting agent in a suitable solvent provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9, n Formula-9 d) condensing the substituted thiophene compound of general formula-10 in-situ with compound of formula-9, 0 Formula-10 (Wherein R = H, OH, X, OR') (X = Halogen, R1 = C1-C4 aliphatic straight chain or branched alkyl group) with a suitable reagent in presence of a suitable base in a suitable solvent provides (S)-5- chloro-N-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide compound of formula-11.

Formula-11 Further the compound of formula-11 can be converted into compound of formula-I by reacting morpholin-3-one in presence of a suitable base in a suitable solvent. Wherein, in step-(a) the solvent is selected from alcoholic solvent, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents, polar aprotic solvents and polar solvents or mixtures thereof; in step-(b) the suitable cyclizing agent is selected from dicyclohexyl carbodiimide (DCC), diisopropylcarbodiimide (DIC), ethyl-(N',N'-dimethylamino) propylcarbodiimide hydrochloride (EDC), N, N-carbonyldiimidazole (CDI) and DABAL-Me3 in presence of a suitable base selected from triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, pyridine, tributyl amine, 4-dimethylamino pyridine, N-methyl morpholine and the like; the suitable solvent is selected from alcoholic solvents, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents or mixtures thereof;

in step-(c) the suitable deprotecting agent is selected from hydrazine hydrate, sodiumboro hydride/acetic acid, methylamine, ethylamine, methanolamine, ethanolamine, 1,2-diaminoethane and the like; the suitable solvent is selected from alcoholic solvents, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents or mixtures thereof; in step-(d) the suitable reagent is selected from pivaloyl chloride, thionyl chloride, phosphorus oxychloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride and the like; and the suitable base is selected from triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, dimethyl formamide, pyridine, tributyl amine, 4-dimethylaminopyridine, N-methyl morpholine and the like; the suitable solvent is selected from alcoholic solvent, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents, polar aprotic solvents and polar solvents or mixtures thereof; The preferred embodiment of the present invention provides a process for the preparation of (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-l ,3-oxazolidin-5-yl)methyl) thiophene-2-carboxamide compound of formula-11 which is a useful intermediate in the synthesis of compound of formula-1, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in a mixture of methanol and water provides (S)-2-(3-(4-fluoro phenylamino)-2-hydroxypropyl) isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with N,N'-carbonyldiimidazole in the presence of dimethylaminopyridine in dichloromethane provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with hydrazine hydrate in dichloromethane provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting 5-chlorothiophene-2-carboxylic acid compound of formula-10b with thionyl chloride in presence of dimethyl formamide in dichloromethane provides 5-chlorothiophene-2-carbonyl chloride compound of general formula-10c,

e) condensing the compound of formula-10c in-situ with compound of formula-9 obtained in step-(c) in dichloromethane provides (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl) thiophene-2-carboxamide compound of formula-11.

The fourth aspect of the present invention is to provide a novel process for the preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in presence or absence of a suitable base in a suitable solvent provides (S)-2-(3-(4-fluorophenylamino)-2-hydroxypropyl)isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with a suitable cyclizing agent in presence of a suitable catalyst in a suitable solvent provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with a suitable deprotecting agent in a suitable solvent provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting the compound of formula-9 with morpholin-3-one in the presence of a suitable base in a suitable solvent provides 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2.

The preferred embodiment of the present invention provides a process for the preparation of 4- {4- [(5 S)-5 -(aminomethyl)-2-oxo-1,3 -oxazolidin-3 -yl]phenyl} morpholin-3 -one compound of formula-2, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in a mixture of methanol and water provides (S)-2-(3-(4-fluoro phenylamino)-2-hydroxypropyl) isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with N,N'-carbonyldiimidazole in the presence of dimethylaminopyridine in dichloromethane provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with hydrazine hydrate in dichloromethane provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting the compound of formula-9 with morpholin-3-one in the presence of a suitable base selected from alkali metal hydroxides, alkali metal alkoxides preferably alkali metal alkoxides such as sodium methoxide, in a suitable solvent selected from alcohol solvents, ester solvents, keto solvents, hydrocarbon solvents and chloro solvents preferably alcohol solvents such as methanol provides 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2,

e) optionally purifying the compound of formula-2 by converting it into acid addition salt compounds of general formula-3 and followed by treating the compound of formula-3 with a suitable base to provide highly pure compound of formula-2.

The compound of formula-2 or its acid addition salt compound of general formula-3 can be further converted into highly pure compound of formula-1 by reacting with 5-chloro thiophene-2-carbonyl chloride compound of formula-10c in a suitable solvent. The fifth aspect of the present invention relates to novel intermediate compounds used for the synthesis of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide compound of formula-1, which are represented by the below mentioned structural formulae:

Formula-8 Formula-11

The 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-l ,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide compound of formula-1 as produced by the present invention can be further micronized or milled to get the desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements. Techniques that may be used for particle size reduction include, but not limited to ball, roller and hammer mills, and jet mills. Milling or micronization may be performed before drying or after the completion of drying of the product. The crystalline acid addition salt compounds of general formula-3 of the present invention are converted into highly pure free base compound of formula-2 using a suitable base.

Further, the highly pure free base compound of formula-2 is useful in the manufacture of highly pure 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide compound of formula-1. PXRD analysis of acid addition salt compounds of general formula-3 of the present invention was carried out using BRUKER/AXS X-ray diffractometer using Cu Ka radiation of wavelength 1.5406 A° at a continuous scan speed of 0.03°/min. Differential scanning calorimetric (DSC) analysis was performed on a Q10 V9.6 Build 290 calorimeter with closed aluminium pans, heating the samples from 40 to 300°C in a dry nitrogen atmosphere at a rate of 10°C/min. HPLC Method of Analysis for Rivaroxaban Intermediates: Apparatus: A liquid chromatographic system is to be equipped with variable wavelength UV-detector; Column: Zorbax SB-C18 15 x 4.6 mm, 5 urn or equivalent. Flow rate: 1.0 ml/min; Wavelength: 240 nm; Column Temperature: 50°C; Injection volume: 5 uL; Run time: 42 min; Diluent: Acetonitrile (100%) Mobile phase; Needle wash: Diluent; Elution: Gradient; Mobile phase: A mixture of 5 ml of orthophosphoric acid (85%), 2 g 1-Octane sulfonic acid sodium salt in 1000 ml of water.

The present invention is schematically represented by following schemes: Scheme-I: The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.

Examples:

Example-1: Preparation of (S)-2-(3-(4-fluorophenylamino)-2-hydroxypropyl)isoindoline-1,3-dione: (Formula-7) 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione (43.8 gm) was added to a mixture of methanol (160 ml), purified water (40 ml) and 4-fluoroaniline (20 g) at 25-30°C. The reaction mixture was stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 60-65°C and then stirred it for 16 hours at the same temperature. After completion of the reaction, the reaction mixture was cooled to 25-30°C and then stirred for 45 minutes at the same temperature. Filtered the precipitated solid and washed with methanol. Further, ethanol (100 ml) was added to the obtained wet compound and stirred for 45 minutes at 25-30°C. Filtered the solid, washed with ethanol and dried to get the title compound; Yield: 45 gms;

Example-2: Preparation of (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl) isoindoline-l,3-dione (Formula-8) (S)-2-(3-(4-fluorophenylamino)-2-hydroxypropyl)isoindoline-l,3-dione (40 gm) was added to a mixture of dichloromethane (200 ml), N,N-carbonyldiimidazole (30.93 gm) and dimethyl amino pyridine (1.5 gm) at 25-30°C. The reaction mixture was heated to 40-45°C and stirred the reaction mixture for 2 hours at the same temperature. After completion of the reaction, distilled off the solvent completely under reduced pressure. Co-distilled the reaction mixture with tetrahydrofuran. Further, tetrahydrofuran (200 ml) was added to the obtained crude and stirred for 10 minutes at 25-30°C. Petroleum ether (400 ml) was added to the reaction mixture and stirred for 10 minutes at 25-30°C. Filtered the precipitated solid, washed with a mixture of tetrahydrofuran and petroleum ether and dried to get the title compound; Yield: 35 gm;

Example-3: Preparation of (S)-5-(aminomethyl)-3-(4-fluorophenyI)oxazoIidin-2-one: (Formula-9) Hydrazine hydrate (25 ml) was added to a mixture of (S)-2-((3-(4-fluorophenyl)-2- oxooxazolidin-5-yl)methyl)isoindoline-l,3-dione (20 gm) and dichloromethane (200 ml) at 25-30°C. The reaction mixture was heated to 40-45°C and stirred for 8 hours at same temperature. After completion of the reaction, filtered the reaction mixture. Distilled off the solvent from the filtrate completely under reduced pressure and then co-distilled with petroleum ether to get title compound; Yield: 11 gms.

Example-4: Preparation of (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl) methyl)thiophene-2-carboxamide: (Formula-11) Thionyl chloride (10.9 gms) was added to a mixture of 5-chlorothiophene-2-carboxylic acid (10 gms), dichloromethane (100 ml) and dimethyl formamide (1.0 ml) at 25-30°C. The reaction mixture was heated to 40-45°C and then stirred the reaction mixture for 2 hours. After completion of reaction, distilled off the solvent from the reaction mixture under reduced pressure. Cooled the reaction mixture to 0-5°C and then added the mixture of (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one obtained in example-3 and dichloromethane (50 ml) to the reaction mixture at the same temperature. Stirred the reaction mixture for 40 minutes at 5°C. After completion of the reaction, slowly triethylamine (10 ml) was added to the reaction mixture at 5°C and stirred the reaction mixture for 30 minutes at the same temperature. Quenched the reaction mixture with purified water and then raised the temperature of the reaction mixture to 20-25°C. Stirred the reaction mixture for 30 minutes at 20-25°C. Filtered the precipitated solid, washed with purified water and petroleum ether and dried to get the title compound. Yield: 15 gms.

Example-5: Preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (Formula-2) Morpholin-3-one (7.2 gms) was added to (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one (15 gms) at 25-30°C. A solution of sodium methoxide (5.7 gms) in methanol (200 ml) was added to the above reaction mixture. Heated the reaction mixture to 40-45°C and stirred for 2 hours at the same temperature. After completion of the reaction mixture, cooled the reaction mixture to 25-30°C and added water (82.5 ml) to the reaction mixture. Stirred the reaction mixture for 30 minutes at 25-30°C. Filtered the precipitated solid, washed with water and dried to get the title compound; Yield: 17.0 gms; Purity by HPLC: 98%.

Example-6: Preparation of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophene carboxamide compound of formula-1 Thionyl chloride (8.7 gms) was added to a mixture of 5-chlorothiophene-2-carboxylic acid (12 gms), dichloromethane (100 ml) and dimethyl formamide (54 ml) at 25-30°C. The reaction mixture was heated to 38-42°C and then stirred the reaction mixture for 2 hours. After completion of reaction, distilled off the solvent from the reaction mixture under reduced pressure. Cooled the reaction mixture to 0-5°C and then added the mixture of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (21.5) and added dichloromethane (100 ml) to the reaction mixture at the same temperature. Stirred the reaction mixture for 40 minutes at 5°C. After completion of the reaction, Quenched the reaction mixture with purified water and then raised the temperature of the reaction mixture to 20-25°C. Stirred the reaction mixture for 30 minutes at 20-25°C. Filtered the precipitated solid, washed with purified water and dried to get the title compound; Yield: 28 gms Particle size distribution (Before micronization): D(0.1) is 8.33 urn; D(0.5) is 36.69 um; D(0.9) is 170.47 um, D(4,3) is 71.32 um; Specific surface area: 0.29 m2/g. Particle size distribution (After micronization): D(0.1) is 3.58 um; D(0.5) is 8.57 um; D(0.9) is 25.15 um, D(4,3) is 12.46 um; Specific surface area: 0.84 m2/g.

Example-7: Preparation of Malate salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (formula-3e): Dichloromethane (100 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (10 gms) at 25-30°C. Heated the reaction mixture to 35-40°C and stirred the reaction mixture for 30 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. A solution of malic acid (4.6 gms) dissolved in methanol (10 ml) was added to the obtained filtrate at 25-30°C. Stirred the reaction mixture for 1 hour at 25-30°C. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound; Yield: 11.4 gms. The PXRD of the obtained compound is shown in figure-7.

Example-8: Preparation of Oxalate salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one(formula-3a): Dichloromethane (100 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3- oxazolidin-3-yl]phenyl} morpholin-3-one (10 gms) at 25-30°C. Heated the reaction mixture to 35-40°C and stirred the reaction mixture for 30 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. A solution of oxalic acid (4.4 gms) dissolved in methanol (10 ml) was added to the obtained filtrate.at 25-30°C. Stirred the reaction mixture for 1 hour at 25-30°C. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound; Yield: 10 gms. The PXRD and DSC of the obtained compound are shown in figures-1&2.

Example-9: Preparation of Maleate salt of 4-{4-[(5S)-5-(aminomethyI)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (formula-3b): Dichloromethane (100 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (10 gms) at 25-30°C. Heated the reaction mixture to 35-40°C and stirred the reaction mixture for 30 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. A solution of maleic acid (4 gms) dissolved in methanol (10 ml) was added to the obtained filtrate at 25-30°C. Stirred the reaction mixture for 1 hour at 25-30°C. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound; Yield: 11.4 gms. The PXRD and DSC of the obtained compound are shown in figures-3&4.

Example-10: Preparation of succinate salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (formula-3c): Dichloromethane (100 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (10 gms) at 25-30°C. Heated the reaction mixture to 35-40°C and stirred the reaction mixture for 30 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. A solution of succinic acid (4 gms) dissolved in methanol (10 ml) was added to the obtained filtrate at 25-30°C. Stirred the reaction mixture for 1 hour at 25-30°C. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound; Yield: 11.4 gms. The PXRD of the obtained compound is shown in figure-5.

Example-11: Preparation of Fumarate salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazoIidin-3-yl]phenyl} morpholin-3-one (formla-3d): Dichloromethane (100 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one (10 gms) at 25-30°C. Heated the reaction mixture to 35-40°C and stirred the reaction mixture for 30 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. A solution of fumaric acid (4 gms) dissolved in methanol (10 ml) was added to the obtained filtrate at 25-30°C. Stirred the reaction mixture for 1 hour at 25-30°C. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound; Yield: 13.2 gms. The PXRD of the obtained compound is shown in figure-6.

Example-12: Preparation of 4-{4-[(5S)-5-(aminoinethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one: (Formula-2) To 10 gms of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one oxalate add dichloromethane (60 ml) and water (60 ml). Basifying the reaction mixture with 10 % aqueous sodium carbonate solution and stirred the reaction mixture for 30 minutes at 25-30°C. Separated the both aqueous and organic phases and distilled off the solvent completely from organic phase under reduced pressure to get the title compound. Yield: 7.4 gms; Purity by HPLC: 99.97%.

Example-13: Preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one: (Formula-2) Dichloromethane (30 ml) and water (30 ml) was added to 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one fumarate (5.0 gms) at 25-30°C. Stirred the reaction mixture for 10 minutes at 25-30°C. Basifying the reaction mixture with 5 % aqueous sodium hydroxide solution and stirred the reaction mixture for 15 minutes at 25-30°C. Separated the both aqueous and organic layers, aqueous layer was extracted with dichloromethane. Combined the organic layers, dried with sodium sulphate and distilled off the solvent completely from organic layer under reduced pressure to get the title compound. Yield: 3.0 gms; Purity by HPLC: 99.95%.

We Claim:

1. A process for the preparation of (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl) thiophene-2-carboxamide compound of formula-11, comprising of; a) reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 Formula-6 in presence or absence of a suitable base in a suitable solvent provides (S)-2-(3 -(4-fluoro phenylamino)-2-hydroxypropyl)isoindoline-1,3-dione compound of formula-7, Formula-7 b) reacting the compound of formula-7 with a suitable cyclizing agent in presence of a suitable catalyst in a suitable solvent provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8, Formula-8 c) reacting the compound of formula-8 with a suitable deprotecting agent in a suitable solvent provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9, Formula-9 d) condensing the substituted thiophene compound of general formula-10 in-situ with compound of formula-9, Formula-10 (Wherein R - H, OH, X, OR') (X = Halogen, R' = C1-C4 aliphatic straight chain or branched alkyl group) with a suitable reagent in presence of a suitable base in a suitable solvent provides (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl) thiophene-2-carboxamide compound of formula-11. Formula-11

2. The process according to claim-1, wherein, in step-(a) the solvent is selected from alcoholic solvent, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents, polar aprotic solvents and polar solvents or mixtures thereof; in step-(b) the suitable cyclizing agent is selected from dicyclohexyl carbodiimide (DCC), diisopropylcarbodiimide (DIC), ethyl-(N',N'-dimethylamino) propyl carbodiimide hydrochloride (EDC), N, N-carbonyldiimidazole (CDI) and DABAL-Me3 in presence of a suitable base selected from triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, pyridine, tributyl amine, 4-dimethylamino pyridine, N-methyl morpholine and the like; the suitable solvent is selected from alcoholic solvents, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents or mixtures thereof; in step-(c) the suitable deprotecting agent is selected from hydrazine hydrate, sodiumboro hydride/acetic acid, methylamine, ethylamine, methanolamine, ethanolamine, 1,2-diaminoethane and the like; the suitable solvent is selected from alcoholic solvents, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents or mixtures thereof; in step-(d) the suitable reagent is selected from pivaloyl chloride, thionyl chloride, phosphorus oxychloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride and the like; and the suitable base is selected from triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, dimethyl formamide, pyridine, tributyl amine, 4-dimethylaminopyridine, N-methyl morpholine and the like; the suitable solvent is selected from alcoholic solvent, ester solvents, ether solvents, hydrocarbon solvents, chloro solvents, polar aprotic solvents and polar solvents or mixtures thereof.

3. A process for the preparation of (S)-5-chloro-N-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl) thiophene-2-carboxamide compound of formula-11, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in a mixture of methanol and water provides (S)-2-(3 -(4-fluoro phenylamino)-2-hydroxypropyl) isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with N,N'-carbonyldiimidazole in the presence of dimethylaminopyridine in dichloromethane provides (S)-2-((3-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with hydrazine hydrate in dichloromethane provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting compound of formula-9 with 5-chlorothiophene-2-carboxylic acid compound of formula-10b Formula-10b in presence of thionyl chloride in dichloromethane and dimethyl formamide provides (S)- 5-chloro-N-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)thiophene-2- carboxamide compound of formula-11.

4. A process for the preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3 yl]phenyl}morpholin-3-one compound of formula-2, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)dione compound of formula-6 in presence or absence of a suitable base in a suitable solvent provides (S)-2-(3-(4-fluorophenylamino)-2-hydroxypropyl) isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with a suitable cyclizing agent in presence of a suitable catalyst in a suitable solvent provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with a suitable deprotecting agent in a suitable solvent provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting the compound of formula-9 with morpholin-3-one in the presence of a suitable base in a suitable solvent provides 4-{4-[(5S)-5-(Aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3 -one compound of formula-2,

e) optionally purifying the compound of formula-2 by converting it into acid addition salt compound of formula-3 by treating it with a suitable acid in a suitable solvent followed by treating the compound of formula-3 with a suitable base in a suitable solvent.

5. A process for the preparation of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-2, comprising of the following steps:

a) Reacting 4-fluoro aniline compound of formula-5 with 2-[(2S)-2-oxiranylmethyl]-lH-isoindole l,3(2H)dione compound of formula-6 in a mixture of methanol and water provides (S)-2-(3-(4-fluoro phenylamino)-2-hydroxypropyl) isoindoline-l,3-dione compound of formula-7,

b) reacting the compound of formula-7 with N,N'-carbonyldiimidazole in the presence of dimethylaminopyridine in dichloromethane provides (S)-2-((3-(4-fluorophenyl)-2-oxo-l,3-oxazolidin-5-yl)methyl)isoindoline-l,3-dione compound of formula-8,

c) reacting the compound of formula-8 with hydrazine hydrate in dichloromethane provides (S)-5-(aminomethyl)-3-(4-fluorophenyl)oxazolidin-2-one compound of formula-9,

d) reacting the compound of formula-9 with morpholin-3-one in the presence of a suitable base selected from alkali metal hydroxides, alkali metal alkoxides preferably alkali metal alkoxides such as sodium methoxide, in a suitable solvent selected from alcohol solvents, ester solvents, keto solvents, hydrocarbon solvents and chloro solvents preferably alcohol solvents such as methanol provides 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound of formula-2.

6. Acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl] phenyl} morpholin-3-one compound of general formula-3 wherein, the acid is selected from inorganic acids such as hydro bromic acid, hydro iodic acid, nitric acid, sulfuric acid and phosphoric acid; and organic acids such as oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphorsulfoic acid, ethane sulfonic acid, gluconic acid, glutaric acid, glutamic acid, methane sulfonic acid, mucic acid, pamoic acid, pantothenic acid, para toluene sulfonic acid and the like.

7. A process for the preparation of acid addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3- oxazolidin-3-yl]phenyl}morpholin-3-one compound of general formula-3, comprising of:

a) Dissolving the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one compound of formula-2 in a first organic solvent such as chloro solvents,

b) dissolving a suitable organic acid in a second organic solvent such as alcoholic solvents and adding the resulting solution to the reaction mixture obtained in step-(a),

c) stirring the reaction mixture,

d) filtering the precipitated solid.

8. A process for the preparation of pure 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl} morpholin-3-one compound of formula-2 comprising of, converting the compound of formula-2 into acid addition salt compounds of general formula-3 by treating it with a suitable acid in a suitable solvent, followed by treating it with a suitable base in a suitable solvent provides pure compound of formula-2.

9. Crystalline forms of acid-addition salts of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}morpholin-3-one compound, wherein;

a) The crystalline oxalic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3a is characterized by,

i) its PXRD pattern substantially in accordance with figure-1,

ii) its powder X-Ray diffractogram having peaks at 5.14, 15.5, 16.9, 17.6, 18.1, 19.6, 19.9,20.3,20.5,23.4,25.6,26.8,28.7, 29.0 and 31.6±0.2 degrees of two-theta, and iii) its DSC thermogram substantially in accordance with figure-2;

b) The crystalline maleic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3b is characterized by,

i) its PXRD pattern substantially in accordance with figure-3,

ii) its powder X-Ray diffractogram having peaks at 4.8, 14.5, 18.37, 18.8, 20.5, 21.1, 21.9,24.5, 24.9,25.529.5 and 34.6±0.2 degrees of two-theta, and iii) its DSC thermogram substantially in accordance with figure-4;

c) The crystalline succinic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3c is characterized by,

i) its PXRD pattern substantially in accordance with figure-5,

ii) its powder X-Ray diffractogram having peaks at 5.8, 11.7, 16.4, 17.6, 19.9, 21.6, 22.0, 23.6, 24.6,26.1,28.7 and 31.5±0.2 degrees of two-theta;

d) The crystalline fumaric acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3d is characterized by,

i) its PXRD pattern substantially in accordance with figure-6,

ii) its powder X-Ray diffractogram having peaks at 2.6, 3.9, 7.9, 14.4, 16.2, 20.6, 24.0, 24.7, 28.6 and 29.3±0.2 degrees of two-theta;

e) The crystalline malic acid salt of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3- yl]phenyl}morpholin-3-one compound of formula-3d is characterized by,

i) its PXRD pattern substantially in accordance with figure-7,

ii) its powder X-Ray diffractogram having peaks at 12.8, 14.5, 14.9, 15.3, 17.2, 17.5, 19.8,21.6,23.0,24.5 and 26.0±0.2 degrees of two-theta.

10. Compounds having the following structural formulae: