DESC:PRIORITY APPLICATION(S)

This application claims priority to Indian Patent Application No. 3786/MUM/2015 filed on October 06, 2015, the disclosures of which is incorporated herein by reference in its entirety as if fully rewritten herein.

FIELD OF THE INVENTION

The invention relates to a process for preparation of 6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-yl compounds, wherein debenzylation reaction is carried at lower temperatures.

BACKGROUND OF THE INVENTION

Compounds of Formula (II) are useful as intermediates in the preparation of various antibacterial compounds. Debenzylation reactions of various 6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl compounds are disclosed in the literature including US Patent Nos. 8,822,450, 8,796,257, 7,112,592, 8,487,093, International Patent Publication Nos. WO 2013038330, WO2014033560, WO2013180197, WO2013149121, and WO2013149136. There is a scope for an improvement in debenzylation reactions of various 6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl compounds. Inventors have surprisingly discovered an improved process for preparation of various 6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-yl compounds (compound of Formula (II)).

SUMMARY OF THE INVENTION

Accordingly, there is provided a process for preparation of a compound of Formula (II), said process comprising debenzylation of a compound of Formula (I) at a temperature between about -20°C to about 15°C;

wherein

A is CN, CONR1R2, CONHNR1R2, CONH-O-R1, optionally substituted heteroaryl;

R1 and R2 are each independently selected from
(a) hydrogen;
(b) a nitrogen protecting group;
(c) C1-C6 alkyl optionally substituted with one or more of the substituents selected from NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NH(cycloalkyl), N(cycloalkyl)2, NH(heterocycloalkyl), N(heterocycloalkyl)2, NH(aryl), N(aryl)2, NH(heteroaryl), or N(heteroaryl)2;
(d) three to seven membered cycloalkyl;
(e) three to seven membered heterocycloalkyl containing at least one heteroatom selected from nitrogen, oxygen and sulfur;
(f) six to fourteen membered aryl; or
(g) five to fourteen membered heteroaryl containing at least one heteroatom selected from nitrogen, oxygen and sulfur.

In one general aspect, there is provided a process for preparation of a compound of Formula (II), said process comprising debenzylation of a compound of Formula (I) in presence of a transition metal catalyst, hydrogen source and suitable solvent at a temperature between about -20°C to about 15°C.

The details of one or more embodiments of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the following description including claims.

DETAILED DESCRIPTION OF THE INVENTION

Reference will now be made to the exemplary embodiments, and specific language will be used herein to describe the same. It should nevertheless be understood that no limitation of the scope of the invention is thereby intended. Alterations and further modifications of the inventive features illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, are to be considered within the scope of the invention. It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise. All references including patents, patent applications, and literature cited in the specification are expressly incorporated herein by reference in their entirety.

The inventors have surprisingly discovered a process for preparation of a compound of Formula (II) from a compound of Formula (I).

The term “C1-C6 alkyl” as used herein refers to branched or unbranched acyclic hydrocarbon radical with 1 to 6 carbon atoms. Typical non-limiting examples of “C1-C6 alkyl” include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, tert-pentyl, neopentyl, sec-pentyl, 3-pentyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl and the like. The “C1-C6 alkyl” may be unsubstituted, or substituted with one or more substituents. Typical, non-limiting examples of such substituents include halogen, alkoxy, CN, SH, COOH, COOC1-C6alkyl, CONH2, OH, NH2, NHCOCH3, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, NHBoc and the like.

The term “cycloalkyl” as used herein refers to three to seven member cyclic hydrocarbon radicals. The cycloalkyl group optionally incorporates one or more double or triple bonds, or a combination of double or triple bonds, but which is not aromatic. Typical, non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. The cycloalkyl may be unsubstituted, or substituted with one or more substituents. Typical, non-limiting examples of such substituents include C1-C6 alkyl, halogen, alkoxy, CN, SH, COOH, COOC1-C6alkyl, CONH2, OH, NH2, NHCOCH3, heterocycloalkyl, heteroaryl, aryl, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, Boc and the like.

The term “aryl” as used herein refers to a monocyclic or polycyclic aromatic hydrocarbon. Typical, non-limiting examples of aryl groups include phenyl, naphthyl, anthracenyl, flourenyl, phenanthrenyl, indenyl and the like. The aryl group may be unsubstituted, or substituted with one or more substituents. Typical, non-limiting examples of such substituents include C1-C6 alkyl, halogen, alkoxy, CN, COOH, CONH2, OH, NH2, NHCOCH3, heterocycloalkyl, heteroaryl, aryl, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, Boc and the like. The term “aryl” includes six to fourteen membered monocyclic or polycyclic aromatic hydrocarbon.

The term “heteroaryl” as used herein refers to a monocyclic or polycyclic aromatic hydrocarbon group wherein one or more carbon atoms have been replaced with heteroatoms selected from nitrogen, oxygen, and sulfur. If the heteroaryl group contains more than one heteroatom, the heteroatoms may be the same or different. Typical, non-limiting example of heteroaryl groups include pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, pyrrolyl, thienyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazonyl, isoxazolyl, oxadiazolyl, oxatriazolyl, isothiazolyl, thiatriazolyl, thiazinyl, oxazinyl, thiadiazinyl, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, tetrazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidyl, tetrahydropyrimidyl, tetrazolo-pyridazinyl, purinyl, benzofuranyl, isobenzofuranyl, benzothienyl, benzothiophenyl, carbazolyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzotriazolyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, acridinyl, naphthothienyl, thianthrenyl, chromenyl, xanthenyl, phenoxathienyl, indolizinyl,indazolyl, phthalazinyl, naphthyridinyl, qinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, beta-carbolinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxazinyl and the like. The heteroaryl group may be unsubstituted, or substituted with one or more substituents. Typical, non-limiting examples of such substituents include C1-C6 alkyl, halogen, alkoxy, CN, COOH, CONH2, OH, SH, SCH3, NH2, NHCOCH3, heterocycloalkyl, heteroaryl, aryl, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, Boc and the like. The term “heteroaryl” includes five to fourteen membered monocyclic or polycyclic aromatic hydrocarbon group containing at least one heteroatom selected from nitrogen, oxygen, and sulfur.

The term “heterocycloalkyl” as used herein refers to three to seven member cycloalkyl group containing one or more heteroatoms selected from nitrogen, oxygen or sulfur. The heterocycloalkyl group optionally incorporates one or more double or triple bonds, or a combination of double bonds and triple bonds, but which is not aromatic. Typical, non-limiting example of heterocycloalkyl groups include aziridinyl, azetidinyl, pyrrolidinyl, 2-oxo-pyrrolidinyl, imidazolidin-2-one-yl, piperidinyl, oxazinyl, thiazinyl, piperazinyl, piperazin-2,3-dione-yl, morpholinyl, thiomorpholinyl, azepanyl, and the like. The heterocycloalkyl may be unsubstituted, or substituted with one or more substituents. Typical, non-limiting examples of such substituents include C1-C6 alkyl, halogen, alkoxy, CN, COOH, CONH2, OH, NH2, NHCOCH3, heteroaryl, aryl, SO2-alkyl, SO2-aryl, OSO2-aryl, Boc and the like. The term “heterocycloalkyl” includes three to seven membered cycloalkyl containing at least one heteroatom selected from nitrogen, oxygen, and sulfur.

The term “halogen” or halo as used herein refers to chlorine, bromine, fluorine or iodine.

The term “nitrogen protecting group” refers to a group which is attached to a nitrogen atom for purpose of protecting a molecule from an undesired reaction of an amine with the reagents used in a chemical reaction. The term ‘”nitrogen protecting groups” as used in herein includes carbobenzyloxy, p-methoxybenzylcarbonyl, tert-butyloxycarbonyl, 9-fluorenyl methyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl, benzyl, carbamate, p-methoxybenzyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, tosyl, and the like.

The term “Boc” as used herein refers to tert-butyloxycarbonyl protecting group.

The term “optionally substituted” as used herein means that substitution is optional and therefore includes both unsubstituted and substituted atoms and moieties. A “substituted” atom or moiety indicates that any hydrogen on the designated atom or moiety can be replaced with a selection from the indicated substituent group, provided that the normal valency of the designated atom or moiety is not exceeded, and that the substitution results in a stable compound.

The inventors have surprisingly found that the debenzylation reactions of 6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-yl compounds at a temperature between about -20°C to about 15°C provides debenzylated compounds in higher yield and greater purity.

In one general aspect, there is provided a process for preparation of a compound of Formula (II), said process comprising debenzylation of a compound of Formula (I) at a temperature between about -20°C to about 15°C;

wherein

A is CN, CONR1R2, CONHNR1R2, CONH-O-R1, optionally substituted heteroaryl;
R1 and R2 are each independently selected from
(a) hydrogen;
(b) a nitrogen protecting group;
(c) C1-C6 alkyl optionally substituted with one or more of the substituents selected from NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NH(cycloalkyl), N(cycloalkyl)2, NH(heterocycloalkyl), N(heterocycloalkyl)2, NH(aryl), N(aryl)2, NH(heteroaryl), or N(heteroaryl)2;
(d) three to seven membered cycloalkyl;
(e) three to seven membered heterocycloalkyl containing at least one heteroatom selected from nitrogen, oxygen and sulfur;
(f) six to fourteen membered aryl; or
(g) five to fourteen membered heteroaryl containing at least one heteroatom selected from nitrogen, oxygen and sulfur.

In some embodiments, there is provided a process for preparation of a compound of Formula (II), said process comprising debenzylation of a compound of Formula (I) at a temperature between about -10°C to about 10°C.

In some embodiments, there is provided a process for preparation of a compound of Formula (IV), said process comprising debenzylation of a compound of Formula (III) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.

In some embodiments, there is provided a process for preparation of a compound of Formula (VI), said process comprising debenzylation of a compound of Formula (V) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.

In some embodiments, there is provided a process for preparation of a compound of Formula (VIII), said process comprising debenzylation of a compound of Formula (VII) at a temperature between about -20°C to about 15°C.

In some embodiments, there is provided a process for preparation of a compound of Formula (X), said process comprising debenzylation of a compound of Formula (IX) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.

In some embodiments, there is provided a process for preparation of a compound of Formula (XII), said process comprising debenzylation of a compound of Formula (XI) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.

In some embodiments, there is provided a process for preparation of a compound of Formula (XIV), said process comprising debenzylation of a compound of Formula (XIII) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.

In some embodiments, there is provided a process for preparation of a compound of Formula (XVI), said process comprising debenzylation of a compound of Formula (XV) at a temperature between about -20°C to about 15°C; wherein R3 is H or nitrogen protecting group.
.
In some embodiments, there is provided a process for preparation of a compound of Formula (XVIII), said process comprising debenzylation of a compound of Formula (XVII) at a temperature between about -20°C to about 15°C.

In some embodiments, said debenzylation reaction is carried out in presence of a transition metal catalyst, hydrogen source and a suitable solvent at a temperature between about -20°C to about 15°C for about 1 hour to about 14 hours. In some embodiments, the transition metal catalyst comprises at least one transition metal selected from palladium, platinum, nickel, ruthenium, rhenium or rhodium. In some other embodiments, transition metal catalyst include 5% palladium on carbon, 10% palladium on carbon, 20% palladium hydroxide on carbon, palladium oxide, palladium black, palladium chloride, platinum over carbon, platinium oxide, Raney-Nickel, rhodium over carbon, ruthenium over carbon, rhenium over carbon, ruthenium oxide and the like.

Typical non-limiting examples of suitable hydrogen source include hydrogen gas, ammonium formate, cyclohexene, lithium - liquid ammonia, ammonia - tert-butanol, sodium - liquid ammonia - tert-butanol, triethyl silyl hydride or a mixture thereof. Typical non-limiting examples of suitable solvent include methanol, ethanol, acetone, dichloromethane, dimethylformamide, ethyl acetate, tetrahydrofuran or a mixture thereof. In some embodiments, the processes according to present invention comprises debenzylation reaction in presence of a 5% palladium over carbon, hydrogen gas and a suitable solvent at a temperature between about -10°C to about 10°C for about 1 hour to about 14 hours.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. For example, those skilled in the art will recognize that the invention may be practiced using a variety of different compounds within the described generic descriptions.

EXAMPLES

The following examples illustrate the embodiments of the invention that are presently best known. However, it is to be understood that the following are only exemplary or illustrative of the application of the principles of the present invention. Numerous modifications and alternative compositions, methods and systems may be devised by those skilled in the art without departing from the spirit and scope of the present invention. The appended claims are intended to cover such modifications and arrangements. Thus, while the present invention has been described above with particularity, the following examples provide further detail in connection with what are presently deemed to be the most practical and preferred embodiments of the invention.

Example 1
Preparation of trans-3-[N’-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-pyrrolidin-1-carboxylic acid tert-butyl ester (IV):

Method A:
To a clear solution of trans-3-[N’-(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-pyrrolidin-1-carboxylic acid tert-butyl ester (III, 5 g, 10.25 mmol) in methanol (50 ml) was added 5% palladium on carbon (0.5 g). The suspension was stirred under atmospheric hydrogen pressure at a temperature of 30°C for 2 hours. The catalyst was filtered over a celite bed and catalyst containing bed was washed with ethyl acetate (25 ml). The filtrate was concentrated under vacuum to provide a white powder, which was triturated with diethylether to provide 2.0 g of trans-3-[N’-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazino carbonyl]-(R)-pyrrolidin-1-carboxylic acid tert-butyl ester (IV) as a white powder in 82% yield.

Method B:
To a clear solution of trans-3-[N’-(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-pyrrolidin-1-carboxylic acid tert-butyl ester (III, 5 g, 10.25 mmol) in methanol (50 ml) was added 5% palladium on carbon (0.5 g). The suspension was stirred under hydrogen gas bubbling below 10°C for 5 hours. The catalyst was filtered over a celite bed and catalyst containing bed was washed with ethyl acetate (25 ml). The filtrate was concentrated under reduced pressure at 40°C to afford 4 g of the titled product (IV) in 100% yield.
Analysis:
Purity as determined by HPLC: 91.8%.

Example 2
Preparation of trans-3-[N’-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-piperidin-1-carboxylic acid tert-butyl ester (VI):

Method A:
To a clear solution of trans-3-[N’-(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-piperidin-1-carboxylic acid tert-butyl ester (V, 16.5 g, 0.033 mol) in methanol (170 ml) was added 10% palladium on carbon (3.55 g). The suspension was stirred under atmospheric hydrogen pressure at a temperature of 30°C for 2 hours. The catalyst was filtered over a celite bed and catalyst containing bed was washed with ethyl acetate (25 ml). The filtrate was concentrated under vacuum to provide a white powder, which was triturated with diethylether to provide 13.5 g of trans-3-[N’-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazino carbonyl]-(R)-piperidin-1-carboxylic acid tert-butyl ester (VI) as a white powder in 100% yield.
Analysis:
Purity as determined by HPLC: 86.45%.

Method B:
To a clear solution of trans-3-[N’-(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl]-(R)-piperidin-1-carboxylic acid tert-butyl ester (V, 100 g, 0.249 mol) in methanol (400 ml) was added 5% palladium on carbon (10 g). The suspension was stirred under hydrogen gas bubbling below 10°C for 2 hours. The catalyst was filtered over a celite bed and same was washed with ethyl acetate (200 ml). The filtrate was concentrated under reduced pressure at 40°C to provide 82 g of trans-3-[N’-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazino carbonyl]-(R)-piperidin-1-carboxylic acid tert-butyl ester (VI) as thick pasty mass in 100% yield.
Analysis:
Purity as determined by HPLC: 94.3%.

Example 3

Preparation of (2S, 5R)-2-carboxamido-6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane (X):

Method A:
To a clear solution of (2S, 5R)-2-carboxamido-6-benzyloxy-7-oxo-1,6-diaza-bicyclo [3.2.1]octane (IX, 7.0 g, 0.025 mol) in a 1:1 mixture of N,N-dimethylformamide and dichloromethane (35 ml: 35 ml) was added 10% palladium on carbon (1.75 g) and hydrogen pressure was applied up to 50 psi. The suspension was shaken for 3 hours at 35°C. The catalyst was removed by filtering the reaction mixture over celite bed. The catalyst bed was washed with dichloromethane (30 ml). Combined filtrate was evaporated under vacuum at a temperature below 40°C to obtain 4.7 g of (2S, 5R)-2-carboxamido-6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane (X) as an oily residue in 100% yield.

Method B:
To a clear solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (IX) (5 g, 18.16 mmol) in methanol (200 ml) was added 5% palladium on carbon (1.5 g). The suspension was stirred under hydrogen gas bubbling below 10°C for 2 hours. The catalyst was filtered over a celite bed and same was washed with ethyl acetate (25 ml). The filtrate was concentrated under reduced pressure at 40°C to provide 3.36 g of product (X) as thick glassy syrup mass in 100% yield.
Analysis:
Purity as determined by HPLC: 99%.

Example 4

Preparation of (2S, 5R)-6-(hydroxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonitrile (VIII):

Method A:
A solution of (2S, 5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonitrile (VII, 1 g, 0.00389 mol) in a mixture of ethyl acetate and tetrahydrofuran (4:6, 4 ml: 6 ml) containing 10% palladium over carbon (0.300 gm, 50% wet) was hydrogenated at 50-55 psi, for 6 hours at 25?C. The resulting mixture was filtered through a celite pad and residue was washed with mixture of ethyl acetate and tetrahydrofuran (4:6, 4 ml: 6 ml). The solvent from the combined filtrate was evaporated under reduced pressure to obtain 0.649 g of (2S, 5R)-6-(hydroxy)-7-oxo-1,6-diaza-bicyclo [3.2.1]octane-2-carbonitrile (VIII) as oil in 100% yield.

Method B:
To a clear solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile (VII) (5 g, 19.43 mmol) in methanol (200 ml) was added 5% palladium on carbon (1.5 g). The suspension was stirred under hydrogen gas bubbling below 10°C for 2 hrs. The catalyst was filtered over a celite bed and same was washing with methanol (25 ml). The filtrate was concentrated under reduced pressure at 40°C to provide 4g of (2S, 5R)-6-(hydroxy)-7-oxo-1,6-diaza-bicyclo [3.2.1]octane-2-carbonitrile (VIII) as thick glassy syrup mass in 93.9% yield.
Analysis:
Purity as determined by HPLC: 93.8%.
,CLAIMS:1. A process for preparation of a compound of Formula (II), said process comprising debenzylation of a compound of Formula (I) at a temperature between about -20°C to about 15°C;

wherein

A is CN, CONR1R2, CONHNR1R2, CONH-O-R1, optionally substituted heteroaryl;

R1 and R2 are each independently selected from
(a) hydrogen;
(b) a nitrogen protecting group;
(c) C1-C6 alkyl optionally substituted with one or more of the substituents selected from NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NH(cycloalkyl), N(cycloalkyl)2, NH(heterocycloalkyl), N(heterocycloalkyl)2, NH(aryl), N(aryl)2, NH(heteroaryl), or N(heteroaryl)2;
(d) three to seven membered cycloalkyl;
(e) three to seven membered heterocycloalkyl containing at least one heteroatom selected from nitrogen, oxygen and sulfur;
(f) six to fourteen membered aryl; or
(g) five to fourteen membered heteroaryl containing at least one heteroatom selected from nitrogen, oxygen and sulfur.

2. A process for preparation of a compound of Formula (IV), said process comprising debenzylation of a compound of Formula (III) at a temperature between about -20°C to about 15°C; wherein R3 is H or a nitrogen protecting group.

3. A process for preparation of a compound of Formula (VI), said process comprising debenzylation of a compound of Formula (V) at a temperature between about -20°C to about 15°C; wherein R3 is H or a nitrogen protecting group.

4. A process for preparation of a compound of Formula (VIII), said process comprising debenzylation of a compound of Formula (VII) at a temperature between about -20°C to about 15°C.

5. A process for preparation of a compound of Formula (X), said process comprising debenzylation of a compound of Formula (IX) at a temperature between about -20°C to about 15°C; wherein R3 is H or a nitrogen protecting group.

6. The process according to any one of Claims 1 to 5, wherein the debenzylation is carried out in presence of a transition metal catalyst and hydrogen source.

7. The process according to Claim 6, wherein the transition metal catalyst comprises at least one transition metal selected from palladium, platinum, nickel, ruthenium, rhenium or rhodium.

8. The process according to Claim 6, wherein the hydrogen source is one or more selected from hydrogen gas, ammonium formate, cyclohexene, lithium - liquid ammonia, ammonia - tert-butanol, sodium - liquid ammonia - tert-butanol or triethyl silyl hydride.

9. The process according to any one of Claims 1 to 8, wherein the process is carried out in presence of solvent selected from methanol, ethanol, dichloromethane, dimethylformamide, ethyl acetate, tetrahydrofuran or a mixture thereof.

10. The process according to any one of Claims 1 to 9, wherein the debenzylation is carried at temperature between about -10°C to about 10°C.