WO2018011721A1

WO2018011721A1 - Novel polymorphic forms of ((1s,2s,3s,4r,5s))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1]oct-1-yl-methanol

Info

Publication number: WO2018011721A1
Application number: PCT/IB2017/054197
Authority: WO
Inventors: Rajashekar BHUPATHI; Prasada Raju Vnkv VETUKURI; Rajesh Kumar Rapolu; Goverdhan Gilla; Krishna Prasad CHIGURUPATI
Original assignee: Granules India Limited
Priority date: 2016-07-15
Filing date: 2017-07-12
Publication date: 2018-01-18

Abstract

The present invention relates to novel polymorph of (( 1 S.2S.3S,4R,5S))-2,3,4-(tris- benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1]oct-1 -yl- methanol of formula (I) wherein Bn refers to benzyl. Characterized by X-ray powder diffraction pattern peaks selected form 5.7, 14.0, 15.6, 15.9, 17.3, 18.8, 19.7, 19.8, 23.0 ±0.2° 2θ. and DSC isothermal peak ranging between 99- 103°C. The invention also relates to process for the preparation of said novel crystalline Form designated as Form-G of ((1S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy- benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1]oct-1-yl-methanol of formula (I). This compound of Formula (I) is useful as an intermediate in the preparation of Ertugliflozin, which is used in the treatment of type 2 diabetes mellitus.

Description

NOVEL POLYMORPHIC FORMS OF (( l S,2S,3S,4R,5S))-2,3,4-(TRiS-BENZYLOXY)- 5-(4-Cl«._JORO-3-(4-ETHOXY-BE ZYL)PiIENYL)-6,8-I.⁾IOXA-BlCYCLO [3.2.1 SOCT-

1 - YL-METHANOL

FIELD OF THE INVENTION

The present invention relates to novel polymorphs of (( l S,2S,3S,4R,5S))-2.3.4-(tris- benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl)phenyl)-6,8-dioxa-bicyclo[3.2.1 ]oct- l -yl- methanol of formula (I).

Formula I

wherein Bn refers to benzyl

The present invention also relates to the use of the novel polymorphs of the present invention in the preparation of SGLT2 inhibitor, specifically Ertugliflozin.

BACKGROUND OF THE INVENTION

((l S,2S,3S,4R,5S))-2,3,4-(Tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl)phenyl)- 6,8-dioxa-bicyclo[3.2.1 ]oct- l -yl-methanol, represented by the following structure formula:

Formula I wherein Bn refers to benzyl . This compound of Formula I is used in the preparation of Ertugliflozin.

Ertugliflozin (PF-04971729. MK 8835), is an investigational SGE 1 -2 Inhibitor which is currently developed by Merck and Pfizer. The structure of Ertugliflozin is shown below:

Formula II

Ertugliflozin was first disclosed in US 8,080,580 B2. This patent also discloses a process for the preparation of Ertugliflozin and its intermediate compound of Formula I, which is shown in the scheme 1 given below:

Scheme I

In US '580 the corresponding compound of Formula I is chromato graphed over silica gel using a gradient of 10 to 30% ethyl acetate in heptane to afford the product as a mixture of isomers (670 mg, 63% yield). This patent neither discloses any physiochemical properties such as PXRD (or) DSC of compound of Formula I. The process disclosed in the above patent is difficult to handle and contains isomeric impurities. Furthermore, chromatography is not preferable for use on an industrial scale. Moreover its isolation and purification is tedious process. The inventors of the present invention developed polymorphic Form of compound of Formula I. Compound of Formula I was being used in the preparation of Ertugliflozin and Ertugliflozin is an important therapeautic agent useful in the treatment of type 2 diabetes mellitus. Additional and improved ways of preparing new polymorphic forms of Compound of Formula I may provide an opportunity to improve the physical characteristics such as purity and crystallinity. Hence, there exists a need for the further development of ne stable crystalline form of Compound of Formula I and commercially viable processes for its preparation, which may be up scalable, safer for handling, less lime consuming and with better and consistent quality parameters.

SUMMARY OF THE INVENTION

Particular aspects of the present invention, it relates to process for the preparation of crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct-l-yl-methanol of Formula (I) characterized by X-ray powder diffraction angle peaks at 5.7, 14.0, 15.6, 15.9, 17.3, 18.8, 19.7, 19.8, 23.0 ±0.2° 2Θ comprising the steps of:

(( l S,2S,3S,4R,5S))-2 ,4-(tris-benzyloxy )-5-(4-chloro-3-(4-etl

Wherein R = CH₃, C₂H₅, Isopropyl, Butyl benzyl ) phenyl) -6, 8-dioxa-bicyclo [3.2. 1 ] oct- l -yl-methanol Bn = Benzyl

Formula III Formula I a. treating compound of formula III with organic acid in an organic solvent; b. isolating ((lS,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4- ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct- 1 -yl-methanol of Formula (I);

c. recrystallizing compound obtained in step b in an organic solvent.

In another particular aspect of the present invention relates to Crystalline Form-G of ((1 S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1] oct- 1 -yl-methanol of Formula (I), characterized by a. X-ray powder diffraction pattern comprising of atleast five diffraction angle peaks selected form 5.7. 14.0. 1 5.6, 1 5.9. 1 7.3. 1 8.8. 1 9.7. 19.8. 23.0 ±0.2° 2Θ;

b. DSC isothermal peak ranging 99- 103°C.

In another particular aspect of the present invention, it relates to Crystalline Form G of

(( l S,2S,3S.4R,5S))-2.3.4-(tris-benzyloxy)-5-(4-chloro-3-(4-etlioxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1 ] oct- l -yl-methanol of Formula (I) useful as an intermediate for the preparation of Ertugliflozin of formula (11). wherein the process comprising treating compound of formula (I) with reducing agent in an organic solvent.

Further particular aspects of the invention are detailed in the description part of the specification, wherever appropriate.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is an example of X-ray powder diffraction ("XRPD") pattern of Crystalline Form-G of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1 ] oct- l -yl-methanol of Formula (I).

Fig. 2 is an example of Differential Scanning Calorimetry ("DSC") curve of Crystalline Form- G of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1] oct-l -yl-methanol of Formula (I).

DETAILED DESCRIPTION OF THE INVENTION

As set forth herein, embodiments of the present invention provide a reproducible and efficient process for the preparation of crystalline Form-G of ((l S,2S,3S,4R,5S))-2,3,4-(tris- benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct- l-yl- methanol of Formula (I).

Formula I

wherein Bn refers to benzyl. In another embodiment of the present invention, it provides a process for the preparation of crystalline Form-G of (( 1 S.2S.3S,4R.5S))-2.3,4-(tris-benzyloxy)-5-(4-chloro-3- (4-ethoxy-benzyl) phenyl) -6.8-dioxa-bicyclo [ 3.2.1 ] oct- 1 -yl-methanol of Formula (1) characterized by X-ray powder diffraction angle peaks at 5.7, 14.0, 1 5.6. 1 5.9, 1 7.3. 1 8.8, 1 9.7. 1 9.8. 23.0 ±0.2° 2Θ comprising the steps of:

erein R = CH-,, C₂H₅, Isopropyl, Butyl

= Benzyl

Formula III Formula I a. treating compound of formula III with organic acid in an organic solvent; b. isolating ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4- ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct- 1 -yl-methanol of

Formula (I);

c. recrystallizing compound obtained in step b in an organic solvent.

In the step of providing a solution according to the present invention, it comprises the source of compound of formula III that may be obtained according any of prior disclosure processes.

In a step of treating compound of formula 111 with organic acid in an organic solvent wherein the organic acid selected from p-Toluenesulfonic acid (PTSA), Sulfanilic acid, 5- Sulfosalicylic acid and organic solvent selected form "Solvent" as defined in the present invention is selected from water or alcohol as Methanol, Ethanol, Propanol, Isopropanol, hydrocarbon solvent as toluene, xylene, heptane, hexane, cyclohexane, or water and/or mixtures thereof. In one of the particular embodiment of the present invention, treating (3S,4S,5R,6S)-

3,4,5-tris(benzyloxy)-6-(4-chloro-3-(4-ethoxy-benzyl)phenyl-6-methoxy tetrahydro-2H- pyran-2„2-diyl) dimethanol with p-toluenesul i nic acid (PTSA) in letrahydrofuran and maintained at temperature 20 - 50°C for 1 5-25 hours. The pH of the sol ution obtained, was adjusted with aqueous solution as 1 0 % sodium hydroxide in water or 1 0 % Potassium hydroxide in water.

In a process step of recovering the crystalline Form-G of (( 1 S.2S.3 S.4R.5S))-2.3,4- (tris-benzyloxy) -5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2. 1 ] oct- 1 -yl- methanol of Formula (I) comprising the following steps:

a. providing solution of ((l S,2S,3S,4R,5S))-2,3.4-(tris-benzyloxy)-5-(4-chloro- 3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct- 1 -yl-methanol of Formula (I) in a solvent or mixture of solvent;

b. isolating the crystalline material;

c. drying under reduced pressure conditions to recover the crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzy!oxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6.8-dioxa-bicyclo [3.2.1 ] oct- 1 -yl-methanol of Formula (I).

In a process step of recovering the crystalline Form-G ((l S,2S,3S,4R,5S))-2,3,4-(tris- benzyloxy) -5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct- l -yl- methanol of Formula (I) was treated with mixture of solvent such as isopropyl alcohol and hexane.

In still another preferred embodiment, the present invention provides a process for preparing crystalline Form-G of compound of Formula I, which comprises the steps of:

a) heating a mixture comprising the compound of Formula 1 with one or more organic solvents to obtain a solution;

b) cooling the solution obtained in step (a);

c) optionally seeding the cooled solution; and

d) recovering the crystalline Form-G of compound of Formula I.

As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise. in another embodiment of the present invention relates to a process for the preparation of Ertugliflozin. which comprises:

i ) de rotecting nov el polymorphs of compound of formula I.

ii) isolating Ertugliflozin crude.

iii) crystallizing Ertugliflozin from one or more of organic solvents. In a preferred embodiment, the crystalline Form-G of compound of Formula-I can be prepared by treating amorphous Form of compound of Formula-1 with one or more organic solvents followed by isolation of crystalline Form-G of compound of Formula-I.

Crystallization may include in a single solvent or mixture of solvents to facilitate the precipitation of the compound of Formula-I. The resulting crystals are then recovered by conventional techniques, such as filtration. They may be washed with water or an organic solvent. The crystals are then preferably dried. The temperature may be increased or the pressure reduced to accelerate the drying process. Drying may be carried out at a suitable temperature.

"Solvent" as defined in the present invention is selected from water or alcohol solvents as Methanol, Ethanol, Propanol, Isopropanol, hydrocarbon solvent as toluene, xylene, heptane, hexane, cyclohexane, esters solvents as ethyl acetate, isopropyl acetate, n-butyl acetate and/or mixtures thereof.

In one of the embodiment of the present invention, crystalline Form-G of ((lS,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1] oct-l-yl-methanol of Formula (I), characterized by X-ray powder diffraction pattern comprising of atleast five diffraction angle peaks selected form 5.758, 8.800, 9.537, 10.518, 1 1.620, 14.079, 15.696, 15.939, 17.391, 18.260, 18.838, 19.782, 19.884, 20.570. 21 .966. 23.01 8. 23.938. 24.763, 24.927. 26.370. 26.745. 27.4. 27.5. 28.299. 29.970. 30.520. 3 1 .284. 3 1 .688. 32. 166. 34.169, 34.993. 35.569, 37.269 ±0.2° 20

In another embodiment of the present invention was crystalline Form-G of (( 1 S.2S,3 S,4R.5S))-2.3.4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl ) -6.8- dioxa-bicyclo [3.2.1 ] oct- l -yl-methanol of Formula ( I), characterized by

a. X-ray powder diffraction pattern comprising of atleast five diffraction angle peaks selected form 5.7, 14.0. 1 5.6, 15.9, 17.3. 1 8.8. 19.7, 19.8, 23.0 ±0.2° 2Θ;

b. DSC isothermal peak ranging 99- 103°C.

The crystalline Form-G of (( l S,2S,3S,4R.5S))-2.3,4-(tris-benzyloxy)-5-(4-chloro-3-(4- ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l -yl-methanol of Formula (I) described herein may be characterized by X-ray powder diffraction pattern (XRPD) and Thermal techniques such as differential scanning calorirnetry (DSC) analysis. The samples of crystalline Form-G of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy- benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct- l -yl-methanol of Formula (1) were analyzed by XRPD on a Bruker AXS D8 Advance Diffractometer using X-ray source— Cu Ka radiation using the wavelength 1 .5418 °A. and lynx Eye detector. DSC was done on a Perkin Elmer instrument. Illustrative examples of analytical data for the crystalline Form-G of formula (I) obtained in the Examples are set forth in the FIGS. 1 -2.

In another embodiment of the present invention, Crystalline Form-G of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [3.2.1 ] oct- l -yl-methanol of Formula (I) is treated with reducing agent selected from Sodium borohydride ( aBH₄), Lindlar catalyst, Diisobutylaluminium hydride (DIBAL- H), Pd/C, Raney Nickel in suitable organic solvents selected from ether solvents as diethylether, tetrahydrofuran, Di-tert-butyl ether, Tert-butyl ether, Methyl tert-butyl ether, alcohol as Methanol, Ethanol, Propanol, Isopropanol, ester solvents as ethyl acetate, diisopropylacetate. Methyl acetate, Isoamyl acetate to get Ertugliflozin of formula (II).

In one of the particular embodiment of the present invention, Crystalline Form-G of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8- dioxa-bicyclo [ 3.2. 1 1 oct- l -yl-methanol of Formula (I) is treated with Pd/C in ethanol and the reaction mixture was maintained for 6 hours at temperature 25-30°C under hydrogen atmosphere. The reaction mass obtai ned was rccrystall ized in ethyl acetate and hexane to gel Hrtugl i ilozin of formula ( I I ).

While the present invention has been described in terms of its specific embodiments. certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The invention is il lustrated below with reference to inventive and comparative example and should not be construed to limit the scope of the invention. EXAMPLES

EXAMPLE 1 : Process for the preparation of Form-G of compound of F rmula- 1

(3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-(4-chloro-3-(4-ethoxy-benzyl)phenyl-6- methoxy tetrahydro-2H-pyran-2,2-diyl) dimethanol (16 g, 0.0216 mol) was added to I I I 1- (8.0 V) at room temperature. Stirred for 5-10 min, then PTSA (3.4 g, 0.0179 mol) was added. Maintained the mass for 18-20 hrs at room temperature. The reaction mass pH was adjusted to 7.0 with sodium bicarbonate solution and the mass was concentrated completely under vacuum. DM water (160 mL) and ethyl acetate (80 mL) was charged to the crude mass. Stirred for 15 min and the layers were separated. Organic layer was washed with sodium chloride solution and dried with sodium sulfate. Concentrated the solvent completely below 50°C under vacuum, furnished light brown syrup mass. The compound was recrystallized from isopropyl alcohol. 48.0 mL isopropyl alcohol was charged and heated to reflux. Maintained 30 min at reflux and cooled to 10-15°C, stirred for 15 hr and filtered. The wet cake was washed with n-hexane (15.0 mL) to obtain Form-G of compound of Formula-I. Yield: 60%;

DSC: 101.94°C;

X-ray powder diffraction pattern angle peaks selected form: 5.758, 8.800, 9.537, 10.518, 1 1.620, 14.079, 15.696, 1 5.939, 17.391 , 1 8.260, 18.838, 19.782, 1 9.884, 20.570, 21 .966, 23.018, 23.938, 24.763, 24.927, 26.370, 26.745, 27.4, 27.5, 28.299, 29.970, 30.520, 31 .284, 31.688, 32.166, 34.169, 34.993, 35.569, 37.269 ±0.2° 20.

EXAMPLE-2: Process for the preparation of Ertugliflozin: The above compound (0.0565 mol. formula-I) was charged lo soh ent mixture of ethyl acetate (5.0 V) and ethanol (5.0V) at room temperature. Then 0.3% ( \vt%) recovery Pd/C was charged under nitrogen atmosphere. The reaction was maintained for 6 hrs at room temperature under hydrogen gas atmosphere. After completion of reaction the mass was filtered on celite bed under nitrogen atmosphere, the filter MLs were concentrated and isolated in ethyl acetate ( 1.0 V ) and n-hexane (6.0 V) to obtain the title compound.

YIELD: 80%

HPLC: 99.2% (by HPLC)

While the foregoing pages provide a detailed description of the preferred embodiments of the invention, it is to be understood thai the summary, description and examples are illustrative only of the core of the invention and non-limiting. Furthermore, as many changes can be made to the invention without departing from the scope of the invention, / is intended that all material contained herein be interpreted as illustrative of the invention and not in a limiting sense.

Claims

We Claim:

1 ) A process for the preparation of crystalline (( 1 S.2S,3S.4R.5 S ))-2.3.4-( tris-benzyloxy )-5- (4-chloro-3-(4-elhoxy-benzyl) phenyl ) -6.8-dioxa-bicyclo [3.2. 1 ] oct- l -yl-methanol of Formula ( I) characterized by X-ray powder diffraction angle peaks at 5.7, 14.0, 15.6. 1 5.9. 1 ° 2Θ comprising the steps of:

-chloro-3-(4-eih l -yl-m eLhanol

Formula III Form ula a. treating compound of formula III with organic acid in an organic solvent;

b. isolating (( l S,2S3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl ) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l -yl-methanol of Formula (I);

c. recrystallizing compound obtained in step b in an organic solvent.

2) The process for the preparation of crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5- (4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l-yl-methanol of Formula (I) according to claim 1 , wherein organic acid is selected from p-Toluenesulfonic acid, Sulfanilic acid, 5-Sulfosalicylic acid.

3) The process for the preparation of crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5- (4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l-yl-methanol of Formula (I) according to claim 1 , wherein organic solvent utilized in step a and step c is selected from alcohol as Methanol, Ethanol, Propanol, Isopropanol, hydrocarbon solvent as toluene, xylene, heptane, hexane, cyclohexane, esters solvents as ethyl acetate, isopropyl acetate, n-butyl acetate, or water and mixtures thereof.

4) The process for the preparation of crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5- (4-chloro-3 -(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l -yl-methanol of Formula (I) according to claim 1 , wherein the process comprising the steps of: a. treating (3S.4S,5R.6S)-3.4,5-lris(benzyloxy)-6-(4-chloro-3-(4-clhoxy- bcnzyl )phenyl-6-methoxy tetrahydro-2I I-pyran-2.2-diyl ) dimethanol with organic acid in an organic solvent and maintained at temperature 20 - 50°C for 1 5-25 hours;

b. adjusting the pH with aqueous solution;

c. recovering the crystalline (( 1 S.2S,3S,4R,5S))-2,3.4-(tris-benzyioxy) -5-(4- chloro-3-(4-ethoxy-benzyl ) phenyl) -6,8-dioxa-bicyclo | 3.2.1 J oct- l -yl- methanol of Formula (I).

5) The process for preparing crystalline ((1 S,2S.3S.4R.5S))-2.3.4-(lris-benzyloxy)-5-(4- chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.24 ] oct- l -yl-methanol of Formula (I) according to claim 4, wherein aqueous solution is selected from sodium hydroxide in water or potassium hydroxide in water.

6) The process for the preparation of crystalline (( 1 S,2S,3S,4R,5S))-2,3.4-(tris-benzyloxy)-5- (4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l -yl-methanol of Formula (I) according to claim 4, wherein Step c of recovering the crystalline material comprises the steps of:

a. providing solution of ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro- 3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1 ] oct-l -yl-methanol of Formula (I) in a solvent or mixture of solvent;

b. isolating the crystalline material;

c. drying under reduced pressure conditions to recover the crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct-l -yl-methanol of Formula (I).

7) Crystalline ((l S,2S,3S,4R,5S))-2,3,4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethoxy-benzyl) phenyl) -6,8-dioxa-bicyclo [3.2.1] oct-l-yl-methanol of Formula (1), designated as Form G, characterized by

a. X-ray powder diffraction pattern comprising of atleast five diffraction angle peaks selected form 5.7, 14.0, 15.6, 15.9, 17.3, 18.8, 19.7, 19.8, 23.0 ±0.2° 2Θ;

b. DSC isothermal peak ranging between 99- 103°C. 8) Crystall ine Form G of ( ( l S.2S $.4R.5S))-2.3.4-(tris-benzyloxy)-5-(4-chloro-3-(4-ethox> - benzyl ) phenyl) -6,8-dioxa-bicyclo | 3.2. 1 ] oct- l -yl-methanol of Formula (I) useful as an intermediate for the preparation of Ertugliflozin, wherein the process for preparing Ertugliflozin comprising treating compound of formula (I) with reducing agent in an organic solvent.

9) The process for the preparation of Ertugliflozin according to claim 8, wherein reducing agent is selected from Sodium borohydride (NaBFE), Lindlar catalyst. Diisobutylaluminium hydride (DIBAL-H), Pd/C, Raney Nickel in suitable organic solvents selected from ether solvents as diethylether, tetrahydrofuran, Di-tert-butyl ether, Tert-butyl ether, Methyl tert- butyl ether, alcohol as Methanol, Ethanol, Propanol, Isopropanol, ester solvents as ethyl acetate, diisopropylacetate. Methyl acetate, Isoamyl acetate to get Ertugliflozin.