DESC:FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of Mirabegron and its intermediates. Mirabegron is chemically described as 2-(2-aminothiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2-phenylethyl]amino}ethyl)phenyl]acetamide. It has the structure of formula I.

I

BACKGROUND OF THE INVENTION
Mirabegron is a selective beta 3-adrenoceptor agonist and which is authorized for the treatment of overactive bladder (OAB) with symptoms of urgency, urgency incontinence and urinary frequency. It is developed and marketed by Astellas Pharma under the brand name MYRBETRIQ TM

Mirabegron and its pharmaceutically acceptable acid addition salts are first disclosed in US 6346532B1 (herein after US’532). The patent US’532 discloses a process for the preparation of Mirabegron as a dihydrochloride salt in an Example- 41 which comprise of deprotection of tert-butyl (R)- N-[2-[4-[2-(2-aminothiazol-4-yl)acetamido]phenyl]ethyl-N-[(2—hydroxy-2-phenyl)ethyl]carbamate (Boc protected Mirabegron) with hydrochloric acid in a mixture of methanol and ethyl acetate followed by purification with reverse phase column chromatography using water/methanol (2:1) as an eluent.

The process for preparation of Mirabegron dihydrochloride is depicted in the following scheme-1.

Scheme-1

The patent US’532 involves the usage of reverse phase column chromatography which is not suggestible for commercial scale. Further dihydrochloride of Mirabegron suffers with strong hygroscopicity and is unstable for use in medication.

Mirabegron free base is disclosed in US 7342117B2 (herein after US’ 1l7). Process for preparation of Mirabegron free base is depicted in the following scheme-2.

Scheme-2

In Chinese patent CN103304511 discloses a process for the preparation of Mirabegron free base as depicted in the following scheme-3.

Scheme-3

In Chinese patent CN103232352 discloses a process for the preparation of Mirabegron free base as depicted in the following scheme-4.

Scheme-4

In Chinese patent publication CN103387500 discloses a process for the preparation of Mirabegron as depicted here in the following scheme-5.

Scheme-5

In Chinese patent CN103864713 discloses a process for the preparation of Mirabegron as depicted in the following scheme-6.

Schem-6

However, the process described in the above for the preparation of Mirabegron is tedious and suffers from many disadvantages like poor yield, low purity and not feasible to economical large scale production.
To overcome this problem, it is necessary to develop a novel and cost effective process for the preparation of large scale production of Mirabegron with high purity.
Thus, the present invention provides a simple, safe and viable process to prepare highly pure Mirabegron using novel intermediates.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (V)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (III);

(b) reacting compound of formula (III) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

In yet another object of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (Va)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (IIIa);

(b) reacting compound of formula (IIIa) with p-toluene sulfonyl chloride in suitable solvent to obtain compound of formula (III);

(c) reacting compound of formula (III) obtained from step (b) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

In yet another object of the present invention is to provide use of compound of formula (III), (IIIa) for the preparation of Mirabegron.

In yet another object of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting (R)-2-amino-1-phenylethan-1-ol of formula (II)

with 4-nitrophenethyl 4-methylbenzenesulfonate of formula (VI)

in the presence of organic base to obtain (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol of formula (VII);

(b) converting compound of formula (VII) obtained from step (a) to Mirabegron of formula (I).

In yet another object of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting tert-butyl (R)-(4-aminophenethyl) (2-hydroxy-2-phenylethyl) carbamate of formula (VIII)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of Hunig’s base and HBTU in DMF to obtain tert-butyl(R)-(4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl)(2-hydroxy-2-phenylethyl)carbamate of formula (IX);

(b) converting compound of formula (IX) obtained from step (a) to Mirabegron of formula (I).

SUMMARY OF THE INVENTION

The main aspect of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (V)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (III);

(b) reacting compound of formula (III) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

In yet another aspect of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (Va)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (IIIa);

(b) reacting compound of formula (IIIa) with p-toluene sulfonyl chloride in suitable solvent to obtain compound of formula (III);

(c) reacting compound of formula (III) obtained from step (b) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

In yet another aspect of the present invention is to provide use of compound of formula (III), (IIIa) for the preparation of Mirabegron.

In yet another aspect of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;

(a) reacting (R)-2-amino-1-phenylethan-1-ol of formula (II)

with 4-nitrophenethyl 4-methylbenzenesulfonate of formula (VI)

in the presence of organic base to obtain (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol of formula (VII);

(b) converting compound of formula (VII) obtained from step (a) to Mirabegron of formula (I).

In yet another aspect of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting tert-butyl (R)-(4-aminophenethyl) (2-hydroxy-2-phenylethyl) carbamate of formula (VIII)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of Hunig’s base and HBTU in DMF to obtain tert-butyl(R)-(4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl)(2-hydroxy-2-phenylethyl)carbamate of formula (IX);

(b) converting compound of formula (IX) obtained from step (a) to Mirabegron of formula (I).

DETAILED DESCRIPTION OF THE INVENTION

The main embodiment of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (V)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (III);

(b) reacting compound of formula (III) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

The reaction step (a) is carried out at 0-5°C and step (b) is carried out at reflux temperature under argon atmosphere.

Suitable base for step (a) & (b) is selected from N-methylmorpholine, pyridine, piperidine, N, N-dimethylaniline, trimethylamine, triethylamine, N, N-Diisopropyl ethylamine (Hunig’s base) and the like.

Suitable solvent for step (a) & (b) is selected from polar aprotic solvents such as for examples, N, N-dimethylformamide, N, N-dimethylacetamide, dimethylsulphoxide, sulpholane, N-methylpyrrolidone or the like; nitrile solvents such as acetonitrile or propionitrile; water or mixture of the said solvents.

Suitable coupling agent for step (a) is selected from N, N’-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1,1’-carbonyldiimidazole (CDI), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HBTU), O-(benzotriazol-1-yl)-N, N, N', N'-tetramethyluronium-tetrafluoroborate (TBTU) and the like.

In yet another embodiment of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (Va)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (IIIa);

(b) reacting compound of formula (IIIa) with p-toluene sulfonyl chloride in suitable solvent to obtain compound of formula (III);

(c) reacting compound of formula (III) obtained from step (b) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

The reaction step (a) is carried out at 0-5°C, step (b) is carried out at room temperature and step (c) is carried out at reflux temperature under argon atmosphere.

Suitable base for step (a) & (c) is selected from N-methylmorpholine, pyridine, piperidine, N, N-dimethylaniline, trimethylamine, triethylamine, N, N-Diisopropyl ethylamine (Hunig’s base) and the like.

Suitable solvent for step (a), (b) & (c) is selected from halogenated hydrocarbons such as dichloromethane, chloroform or chlorobenzene; polar aprotic solvents such as for examples, N, N-dimethylformamide, N, N-dimethylacetamide, dimethylsulphoxide, sulpholane, N-methylpyrrolidone or the like; nitrile solvents such as acetonitrile or propionitrile; water or mixture of the said solvents

Suitable coupling agent for step (a) is selected from N, N’-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1,1’-carbonyldiimidazole (CDI), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HBTU), O-(benzotriazol-1-yl)-N, N, N’, N'-tetramethyluronium-tetrafluoroborate (TBTU) and the like.

In yet another embodiment of the present invention is to provide use of compound of formula (III), (IIIa) for the preparation of Mirabegron.

In yet another embodiment of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting (R)-2-amino-1-phenylethan-1-ol of formula (II)

with 4-nitrophenethyl 4-methylbenzenesulfonate of formula (VI)

in the presence of organic base to obtain (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol of formula (VII);

(b) converting compound of formula (VII) obtained from step (a) to Mirabegron of formula (I).

The reaction step (a) is carried out at reflux temperature and suitable organic base for step (a) is selected from N-methylmorpholine, pyridine, piperidine, N, N-dimethylaniline, trimethylamine, triethylamine, N, N-Diisopropyl ethylamine (Hunig’s base) and the like.

In yet another embodiment of the present invention is to provide a process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting tert-butyl (R)-(4-aminophenethyl) (2-hydroxy-2-phenylethyl) carbamate of formula (VIII)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of Hunig’s base and HBTU in DMF to obtain tert-butyl(R)-(4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl)(2-hydroxy-2-phenylethyl)carbamate of formula (IX);

(b) converting compound of formula (IX) obtained from step (a) to Mirabegron of formula (I).

The reaction step (a) is carried out at 0-5°C under argon atmosphere. In step (b) deprotection of Boc-protected Mirabegron is carried out by using HCl to obtain Mirabegron 2HCl which is solubilized in water and basified with NaOH to obtain Mirabegron.

The process of present invention is depicted in following schemes.

SCHEME - I

SCHEME – II

SCHEME – III

SCHEME – IV

The following examples illustrate the present invention and as such are not being considered as limiting the invention set forth in the claims appended hereto.

EXAMPLES
Example-1 Preparation of 2-(2-aminothiazol-4-yl)-N-(4-(2-bromoethyl)phenyl) acetamide of formula (III, wherein X is Br)
To 2 gm (1 eqv) of 4-(2-bromoethyl)aniline in 15 ml of DMF at 0°C was added 4.171 g (1.1 eqv) of HBTU and 1.898 gm (1.2 eqv) of 2-(2-aminothiazol-4-yl) acetic acid under argon followed by 2.2 ml (1.3 eqv) of Hunig’s base and left stirring over 2.5 hrs at 0-5°C. Quench the reaction mixture with water, extract with EA, wash 3 x H2O, dried and concentrated. Purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 2.97 gm of 2-(2-aminothiazol-4-yl)-N-(4-(2-bromoethyl)phenyl)acetamide in 87% yield.

Example-2 Preparation of 4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl 4-methylbenzenesulfonate of formula (III wherein X is OTs)
To 5 gm (1 eqv) of 4-aminophenethyl 4-methylbenzenesulfonate in 45 ml of DMF at 0°C was added 7.34 gm (1.1 eqv) of HBTU and 3.2 g (1.15 eqv) of 2-(2-aminothiazol-4-yl) acetic acid under argon followed by 3.7 ml (1.2 eqv) of Hunig’s base and left stirring over 2 hrs at 0-5°C. When the reaction is over by HPLC, quench the reaction mixture with water, extract with EA, wash 5 x H2O, followed by a wash with 1M HCl (50 ml). The organic phase was washed with once with NaHCO3 solution, dried and taken to dryness to obtain 5.82 gm of 4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl 4-methylbenzenesulfonate in 77% yield and in 97% purity.

Example-3 Preparation of 2-(2-aminothiazol-4-yl)-N-(4-(2-hydroxyethyl)phenyl) acetamide of formula (IIIa)
To 5 gm (1 eqv) of 2-(4-aminophenyl)ethan-1-ol in 45 ml of DMF at 0°C was added 7.34 g (1.1 eqv) of HBTU and 3.2 gm (1.15 eqv) of 2-(2-aminothiazol-4-yl)acetic acid under argon followed by 3.7 ml (1.2 eqv) of Hunig’s base and left stirring over 2 hrs at 0-5°C. When the reaction is over by HPLC, quench the reaction mixture with water, extract with EA, wash 5 x H2O, followed by a wash with 1M HCl (50 ml). The organic phase was washed with once with NaHCO3 solution, dried and taken to dryness to obtain 5.82 gm of 2-(2-aminothiazol-4-yl)-N-(4-(2-hydroxyethyl)phenyl) acetamide in 77% yield and in 97% purity.

Example-4 Preparation of 4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl 4-methylbenzenesulfonate of formula (III wherein X is OTs)
To 1.0 gm (1 eqv) of 2-(2-aminothiazol-4-yl)-N-(4-(2-hydroxyethyl)phenyl) acetamide in 18 ml of DCM was added under argon 0.82 gm (1.2 eqv) of TsCl at RT and left stirring overnight. After the reaction is over by TLC. Quenched the reaction with 10 ml of MeOH followed by water and extracted in DCM. Washed the organic layer with water and brine, dried and evaporated to dryness to obtain solid which was slurred in 60 ml of acetonitrile over 5 minutes. Then filtered the solid to obtain 0.4 gm of the 4-(2-(2-aminothiazol-4-yl) acetamido)phenethyl 4-methyl benzene sulfonate.

Example-5 Preparation of Mirabegron of formula (I)
To 44 mg (1 eqv) of (R)-2-amino-1-phenylethan-1-ol in 2 ml of Acetonitrile was added 109 mg (1 eqv) of 2-(2-aminothiazol-4-yl)-N-(4-(2-bromoethyl)phenyl)acetamide followed by 300 µl of Et3N and left refluxing at 85°C overnight under argon. Next day another equivalent of 2-(2-aminothiazol-4-yl)-N-(4-(2-bromoethyl) phenyl)acetamide was added into the reaction mixture for a total of 2 equivalents and continued refluxing another 5 hrs. Quenched the reaction mixture with 10 ml of water. Extracted with EA, washed with water and brine. Dried and purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 64 mg of pure Mirabegron in 54% yield.

Example-6 Preparation of Mirabegron of formula (I)
To 350 mg (1 eqv) of (R)-2-amino-1-phenylethan-1-ol in 20 ml of Acetonitrile was added 770 mg (1 eqv) of 4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl 4-methylbenzenesulfonate followed by 500 µl of Et3N and left refluxing at 85°C overnight under argon. Next day quenched the reaction mixture with 20 ml of water. Extracted with EA, washed with water and brine. Dried and taken to dryness and purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 404 mg of pure Mirabegron in 40% yield.

Example-7 Preparation of tert-butyl (R)-(2-hydroxy-2-phenylethyl)(4-nitrophenethyl) carbamate
To 0.874 gm (1 eqv) of (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol in 15 ml of THF was added 1.64 ml (2 eqv) of 2.5N NaOH at RT followed by 0.8 g (1.2 eqv) of Boc anhydride and left stirring under argon over 1.5 hrs. Quenched the reaction with 3 ml of MeOH and water. Extracted with EA, washed with water and brine. Dried and taken to dryness and purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 1.075 g of tert-butyl (R)-(2-hydroxy-2-phenylethyl)(4-nitrophenethyl) carbamate in 91% yield.

Example-8 Preparation of tert-butyl (R)-(4-aminophenethyl)(2-hydroxy-2-phenylethyl) carbamate of formula (VIII)
To 0.931 gm (1 eqv) of tert-butyl (R)-(2-hydroxy-2-phenylethyl)(4-nitrophenethyl) carbamate in 15 ml of MeOH was added 0.093 gm of 10% Pd/C and hydrogenated by bubbling H2 gas and stirred until the reaction was over. Once the reaction was over by TLC, filtered on celite, evaporated to dryness to obtain 0.80 gm of tert-butyl (R)-(4-aminophenethyl)(2-hydroxy-2-phenylethyl) carbamate in 94% yield.

Example-9 Preparation of tert-butyl(R)-(4-(2-(2-aminothiazol-4-yl)acetamido) phenethyl) (2-hydroxy-2-phenylethyl)carbamate of formula (IX)
To 0.664 gm (1 eqv) of tert-butyl (R)-(4-aminophenethyl)(2-hydroxy-2-phenylethyl) carbamate in 7 ml of DMF at 0°C was added 0.777 gm (1.1 eqv) of HBTU and 0.353 gm (1.2 eqv) of 2-(2-aminothiazol-4-yl) acetic acid under argon followed by 0.4 ml (1.25 eqv) of Hunig’s base and left stirring over 2.5 hrs at 0-5°C. Quench the reaction mixture with water, extract with EA, wash 3 x H2O, dried and concentrated. Purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 0.839 g of bocylated Mirabegron in 91% yield.

Example-10 Preparation of Mirabegron of formula (I)
0.839 gm of Bocylated Mirabegron was deprotected and precipitated as it’s hydrochloride salt by the addition of 10 ml HCl in ether (2M) at 0-5°C during the addition and then stirred at RT for an additional 2 hrs. Filtered the ppt and washed with ether, dried under vacuum to obtain 0.713 gm of Mirabegron 2HCl in 90% yield.
2.4 gm of Mirabegron 2HCl was solubilized in 50 ml of water and basified to pH 9-10 with 3M NaOH with cooling, followed by 100 ml of EA and left stirring over 1hrs at RT. Then separated the phases. Dried the organic phase until the volume of EA was 5 ml and added 150 ml of ether and left stirring the pasty product over 3 to 4 hrs until it solidified. added 15 ml of acetonitrile into the mixture and left stirring overnight at RT, filter the solid to obtain 98% pure Mirabegron in 77% yield.

Example-11 Preparation of (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol of formula (VII)
To 4.27 gm (1eqv) of (R)-2-amino-1-phenylethan-1-ol in 22 ml of Et3N was added 10 gm (1 eqv) of 4-nitrophenethyl 4-methylbenzenesulfonate and heated the mixture to reflux over 1 hr. After 1 hr. another 1 gm (0.1eqv) of 4-nitrophenethyl 4-methylbenzenesulfonate was added and continued refluxing. Repeat the same after the 2nd hour for a total of 1.2 eqv. of 4-nitrophenethyl 4-methylbenzenesulfonate. After 3 hrs. cooled the mixture to RT and quenched with water and DCM. Extracted with DCM, washed with 2 x H2O, dried and concentrated on a rotavapour to obtain an orange viscous oil which was purified by silica gel column chromatography (eluent: DCM/MeOH) to obtain 5.4 g of (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol in 61% yield. ,CLAIMS:We claim:

1. A process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (V)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (III);

(b) reacting compound of formula (III) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

2. A process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting compound of formula (Va)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of base and coupling agent in suitable solvent to obtain compound of formula (IIIa);

(b) reacting compound of formula (IIIa) with p-toluene sulfonyl chloride in suitable solvent to obtain compound of formula (III);

(c) reacting compound of formula (III) obtained from step (b) with (R)-2-amino-1-phenylethan-1-ol of formula (II)

in the presence of base in suitable solvent to obtain Mirabegron of formula (I).

3. The process as claimed in claim 1 & 2, wherein suitable base is selected from N-methylmorpholine, pyridine, piperidine, N, N-dimethylaniline, trimethylamine, triethylamine, N, N-Diisopropyl ethylamine (Hunig’s base) and the like.

4. The process as claimed in claim 1 & 2, wherein suitable solvent is selected from halogenated hydrocarbons such as dichloromethane, chloroform or chlorobenzene; polar aprotic solvents such as for examples, N, N-dimethylformamide, N, N-dimethylacetamide, dimethylsulphoxide, sulpholane, N-methylpyrrolidone or the like; nitrile solvents such as acetonitrile or propionitrile; water or mixture of the said solvents

5. The process as claimed in claim 1 & 2, wherein suitable coupling agent is selected from N, N’-dicyclohexylcarbodiimide(DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC), 1,1’-carbonyldiimidazole(CDI), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium
hexa fluorophosphate(HBTU), O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium-
tetrafluoroborate(TBTU) and the like.

6. Use of compound of formula (III), (IIIa) for the preparation of Mirabegron.

7. A process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting (R)-2-amino-1-phenylethan-1-ol of formula (II)

with 4-nitrophenethyl 4-methylbenzenesulfonate of formula (VI)

in the presence of organic base to obtain (R)-2-((4-nitrophenethyl) amino)-1-phenylethan-1-ol of formula (VII);

(b) converting compound of formula (VII) obtained from step (a) to Mirabegron of formula (I).

8. The process as claimed in claim 7, wherein suitable organic base is selected from N-methylmorpholine, pyridine, piperidine, N, N-dimethylaniline, trimethylamine, triethylamine, N, N-diisopropylethylamine (Hunig’s base) and the like.

9. A process for the preparation of Mirabegron of formula (I) which comprises steps of;
(a) reacting tert-butyl (R)-(4-aminophenethyl) (2-hydroxy-2-phenylethyl) carbamate of formula (VIII)

with 2-(2-aminothiazol-4-yl) acetic acid of formula (IV)

in the presence of Hunig’s base and HBTU in DMF to obtain tert-butyl(R)-(4-(2-(2-aminothiazol-4-yl)acetamido)phenethyl)(2-hydroxy-2-phenylethyl)carbamate of formula (IX);

(b) converting compound of formula (IX) obtained from step (a) to Mirabegron of formula (I).