FIELD OF THE INVENTION
The present invention relates to an improved process to prepare Rosuvastatin calcium of Formula I.

BACKGROUND OF THE INVENTION
Rosuvastatin, which is an antihyperchlolesterolemic drug, is chemically known as (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimid" in-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoic acid calcium (2:1) sah of Formula I.
Rosuvastatin is enantiomerically pure compound having two chiral centers in the side chain of the molecule. All four isomers of Rosuvastatin can be separated by HPLC.
The synthetic process for preparing Rosuvastatin Calcium is disclosed in US RE 37,314 E, which involves reduction of 5-keto-3(R)-hydroxy rosuvastatin methyl ester using sodium borohydride and diethylmethoxyborane in presence of tetrahydrofuran and methanol.
WO 2006/100689 Al discloses a process to prepare rosuvastatin alkyl ester from rosuvastatin keto ester by combining rosuvastatin keto ester, diethylmethoxy borane in tetrahydrofuran and methanol. Thereafter, sodium borohydride was added to the above reaction mass and stirred to obtain rosuvastatin alkyl ester.

HPLC analysis of the Rosuvastatin alkyl ester produced by the methods disclosed in the above references revealed that the reduction did not go to completion and the resulting Rosuvastatin alkyl ester is contaminated with unreacted starting material and also high level of diastereomeric impurity. It is tedious to separate these impurities by the conventional purification techniques. Therefore, we realized that there is a need for reduction, which gives pure Rosuvastatin alkyl ester.
WO 2007/040940 A1 discloses a process to prepare rosuvastatin alkyl ester from rosuvastatin keto ester by combining MeO-9-BBN or diethylmethoxyborane with an organic solvent selected from a group consisting of methylene chloride, toluene, methyl t-butyl ether, diethyl ether, tetrahydrofuran, dioxane, methanol, ethanol, isopropanol, n-butanol; and a source of hydride ion and then adding to the said combination to a solution of a rosuvastatin keto ester in an organic solvent to obtain a reaction mixture. Thereafter, the reaction mixture was maintained to obtain rosuvastatin alkyl ester. Analysis of the product obtained by the above process revealed that the presence of unreacted starting material in the product, which was difficult to separate by normal crystallization techniques.
Therefore, we report herein a process to prepare Rosuvastatin alkyl esters having low level of diastereomeric impurity and other impurities, which can give Rosuvastatin calcium with desired quality.
OBJECTIVE
The objective of the present invention is to provide an improved process for preparing Rosuvastatin calcium with high yield and high purity.
In yet another objective of the present invention is to provide an improved process for preparing Rosuvastatin, which is simple, industrially applicable and economically viable.

SUMMARY OF THE INVENTION
The present invention relates to an improved process for preparing Rosuvastatin alkyl ester of Formula II,

wherein R represents straight or branched C1-5 alkyl, aryl, aralkyl which comprises:
a) reducing Rosuvastatin keto ester of Formula III

with a hydride ion source and dialkylalkoxyborane at low temperature in a mixture of three or more organic solvents selected each from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) maintaining the reaction mass at the same temperature under stirring for completion of reaction;
c) isolating the compound of Formula II.
The present invention also relates to an improved process for preparing Rosuvastatin alkyl ester of Formula II,


wherein R represents straight or branched C1-5 alkyl, aryl, aralkyl which comprises:
a) combining Rosuvastatin keto ester of Formula III

with dialkylalkoxyborane at low temperature in a mixture of three or more organic solvents selected each from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) adding hydride ion source at temperature ranging from -50°C to -90°C to
step (a) mixture;
c) maintaining the reaction mass at the same temperature under stirring for
completion of reaction;
d) quenching the reaction mass with water or acids such as acetic acid,
trifluoroacetic acid or bases like aqueous sodium bicarbonate, potassium
carbonate or peroxide like aqueous hydrogen peroxide and the like to
obtain compound of Formula II.
The present invention also relates to an improved process for preparing Rosuvastatin alkyl ester of Formula II,


wherein R represents straight or branched C1.5 alkyl, aryl, aralkyl which comprises:
a) combining dialkylalkoxyborane, hydride ion source at low temperature in a mixture of three or more organic solvents selected each from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) adding a solution of Rosuvastatin keto ester of Formula III

to step (a) mixture;
c) maintaining the reaction mass at the same temperature under stirring for completion of reaction;
d) quenching the reaction mass with water or acids such as acetic acid, trifluoroacetic acid or bases like aqueous sodium bicarbonate, potassium carbonate or peroxide like aqueous hydrogen peroxide and the like to obtain compound of Formula II.
In another embodiment, the present invention also provides further conversion of Rosuvastatin alkyl ester of Formula II to Rosuvastatin calcium, with high purity.

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an improved process for the preparation of Rosuvastatin alkyl ester of Formula II, which comprises preparing a solution of Rosuvastatin keto ester of Formula III in an organic solvent or a mixture of organic solvents and adding a solution of dialkylalkoxyborane in a mixture of three or more organic solvents at low temperature to the above solution. Thereafter, the reaction mass is stirred at same temperature and treated with a source of hydride ion. The organic solvent is selected from the group consisting of an ethereal solvent selected from C2-C8 ethers or cyclic ethers such as diethyl ether, dimethyl ether, tetrahydrofuran; alcoholic solvent selected from C1-C4 alcohol such as methanol, ethanol, butanol and aprotic solvents such as toluene, alkyl esters such as ethyl acetate, methyl acetate, chlorinated solvents such as methylene chloride, chloroform.
The present invention relates to an improved process for the preparation of Rosuvastatin alkyl ester of Formula II, which comprises providing a solution of dialkylalkoxyborane and source of hydride ion at low temperature in a mixture of three or more organic solvents. Dissolving Rosuvastatin keto ester of Formula III in an organic solvent or a mixture of organic solvents and adding this solution to above solution at low temperature. Thereafter, the reaction mass is stirred to yield Rosuvastatin alkyl ester of Formula II. The organic solvent is selected from the group consisting of an ethereal solvent selected from C2-C8 ethers or cyclic ethers such as diethyl ether, dimethyl ether, tetrahydrofuran; alcoholic solvent selected from C1-C4 alcohol such as methanol, ethanol, butanol and aprotic solvents such as toluene, alkyl esters such as ethyl acetate, methyl acetate, chlorinated solvents such as methylene chloride, chloroform.
The dialkylalkoxyborane is selected from diethylmethoxyborane, dimethylmethoxyborane, diethylethoxyborane, dimethylethoxyborane. Preferably diethylmethoxyborane is used as chelating agent.

A solution of dialkylalkoxyborane is prepared by adding a tetrahydrofuran solution of dialkylalkoxyborane to a solvent mixture selected from the group consisting of an ethereal solvent selected from C2-C8 ethers or cyclic ethers such as diethyl ether, dimethyl ether, tetrahydrofuran; alcoholic solvent selected from C1-C4 alcohol such as methanol, ethanol, butanol and aprotic solvents such as toluene, alkyl esters such as ethyl acetate, methyl acetate, chlorinated solvents such as methylene chloride, chloroform; or mixture of three or more solvents.
The three preferred solvents are tetrahydrofuran, methanol and ethyl acetate or tetrahydrofuran, methanol and toluene. The chelating agent used is in the range of 1-10 m. eq. based on Rosuvastatin keto ester of Formula III.
Preferably, the total volume of solvent used for the preparation of Rosuvastatin keto ester of Formula III and dialkylalkoxyborane is about 10 volumes to 80 volumes (ml per gram of Rosuvastatin keto ester of Formula III) in the reaction mixture, more preferably 30-40 volumes.
Source of hydride ion is selected from a group consisting of sodium borohydride, potassium borohydride, lithium borohydride and sodium triacetoxyborohydride preferably the source of hydride ion is present in an amount of 1 to about 4 equivalent (per gram of Rosuvastatin keto ester of Formula III). The solvents used in the present invention should not decompose hydride ion source.
The temperature during the mixing of Rosuvastatin keto ester of Formula III solution with diethylmethoxyborane solution and also while adding hydride ion source is preferably in the range of-50°C to -95°C, more preferably -70°C to -80°C.
The reaction mixture is maintained for 30 min to 8 h; preferably 5-6 h at temperature -70°C to -80°C.
Reaction is quenched at -80°C to -50°C by adding quenching agent to the reaction mass. The quenching agent is selected from water, acetic acid, aqueous

hydrochloric acid, acetone, trifluoroacetic acid, aqueous hydrogen peroxide, ammonium chloride, sodium bicarbonate, aqueous acidic buffer or mixture thereof. Preferred agents are acidic buffer or acetic acid.
Aqueous acidic buffer is made from potassium dihydrogen phosphate, triethyl amine and orthophosphoric acid having pH in range of 2-4.
After quenching the reaction, the reaction mass is diluted with water and extracted with solvents like ethyl acetate, toluene, methylene chloride and the like and preferably with ethyl acetate.
Another embodiment of the invention provides a process for improving the quality of the Rosuvastatin alkyl ester of Formula II, by recrystallization.
The recrystallization process of Rosuvastatin alkyl ester of Formula II, comprises: a) preparing a solution of Rosuvastatin alkyl ester of Formula II, in an organic solvent selected from C1-C5 alcohol such as methanol, ethanol, butanol; C3-C8 esters such as ethyl acetate, methyl acetate; C3-C8 ketones such as methylethyl ketone, methylisobutyl ketone, acetone; C6-C10 aromatic hydrocarbons such as toluene; ethers such as tetrahydrofuran, methylethyl ether; acetonitrile and mixture thereof and cooling the mass to give Rosuvastatin alkyl ester of Formula II.
Another recrystallization process of Rosuvastatin alkyl ester of Formula II, which
comprises:
a) preparing a solution of Rosuvastatin alkyl ester of Formula II, in an organic solvent selected from C1-C5 alcohol such as methanol, ethanol, butanol; C3-C8 esters such as ethyl acetate, methyl acetate; C3-C8 ketones such as methylethyl ketone, methylisobutyl ketone, acetone; C6-C10 aromatic hydrocarbons such as toluene, anisole; ethers such as tetrahydrofuran, methylethyl ether; acetonitrile and mixture thereof;

b) treating the above solution from step (a) with an anti solvent like aliphatic hydrocarbons like, pentane, hexane, heptane, cyclohexane and the like;
c) stirring the resulting slurry from step (b) for 1 h to 48 h to give pure Rosuvastatin alkyl ester;
d) collecting the resulting pure Rosuvastatin alkyl ester.
In the slurry method, the temperature in step (c) is maintained at 0-50°C preferably between 20-30°C.
This present process provides a method for preparing alkyl esters of Rosuvastatin with low levels of impurities.
The present invention provides a process for preparing Rosuvastatin having low levels of diastereomeric impurity and other contaminants like Rosuvastatin keto ester of Formula III.
The preparation of Rosuvastatin keto ester of Formula III, is elaborated in our co¬pending application numbers 1994/CHE/2006 and 1121/CHE/2007 filed in Chennai, India.
The invention is illustrated with the following examples, which are provided by way of illustration only and should not be construed to limit the scope of the invention.

EXAMPLE-1
PREPARATION OF (+) ETHYL 7-[4-(4-FLUOROPHENYL)-6-
ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)
PYRIMIDIN-5-YL]-(3R,5S)-3,5-DIHYDROXY-6(E)-HEPTENOATE
(ROSUVASTATIN ETHYLESTER)
A solution of diethylmethoxyborane in tetrahydrofuran was added (5.24 ml, 4.062 M solution in tetrahydrofuran) to a cold mixture of tetrahydrofuran (60 ml), methanol (13 ml) and ethyl acetate (5 ml) at -75°C to -80°C. After stirring this mass for 5 min, a solution of ethyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-3-oxo-5(S)-hydroxy-6(E)-heptenoate (2g) prepared in a mixture of tetrahydrofuran (5 ml), methanol (2 ml) and ethyl acetate (3 ml) was added to the above borane solution, while maintaining the temperature at -75°C to -80°C.
Solid sodium borohydride (0.48 g) was added to the above mixture and the
resulting mass was stirred at -75°C to -80°C for 5-6 h to ensure completion of
reduction. The reaction mass was worked-up and purified from ethyl acetate and
heptane.
Yield: 0.8 g
Purity: 99.04 %
Anti isomer: 0.42 %
EXAMPLE-2
PREPARATION OF (+) ETHYL 7-[4-(4-FLUOROPHENYL)-6-
ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)
PYRIMIDIN-5-YL]-(3R,5S)-3,5-DIHYDROXY-6(E)-HEPTENOATE
(ROSUVASTATIN ETHYLESTER)
A solution of ethyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N)-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-3-oxo-5(S)-hydroxy-6(E)-heptenoate (30 g)

in a mixture of tetrahydrofuran (75 ml), methanol (30 ml) and ethyl acetate (45 ml) was added to a cold solution of diethylmethoxyborane (17.5 ml of 4,06 M solution in tetrahydrofuran) prepared in a mixture of tetrahydrofuran (900 ml), methanol (195 ml) and ethyl acetate (75 ml) at -75°C to -80°C under stirring. Solid sodium borohydride (3.378 g) was added to the above mixture and stirred for 5-6 h for complete reduction. To the reaction mass sequentially added acetone (10 ml) followed by acetic acid (43 ml), water (500 ml), ethyl acetate (300 ml) and allowed to warm to room temperature. The layers were separated and the aqueous layer was extracted second time with ethyl acetate (300 ml). The combined organic layer was washed with brine solution followed by water. The crude product obtained after evaporation of ethyl acetate was co-distilled twice with methanol and crystallized from a mixture of ethyl acetate, ethanol and heptane. Yield: 24.8 g Purity: 99.28 % Anti isomer: 0.48 % Rosuvastatin keto-ester: Nil
EXAMPLE-3
PREPARATION OF (+) ETHYL 7-[4-(4-FLUOROPHENYL)-6-
ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)
PYRIMIDIN-5-YL]-(3R,5S)-3,5-DIHYDROXY-6(E)-HEPTENOATE
(ROSUVASTATIN ETHYLESTER)
A mixture of tetrahydrofuran (60 ml), methanol (13 ml) and toluene (5 ml) was cooled to -78°C under nitrogen. Diethylmethoxyborane (1.2 ml, 48% w/w in tetrahydrofuran) was added drop wise to the above reaction mixture at -75 °C to -78°C over a period of 5 min. The mixture was stirred for 5 min at -75°C to -78°C and a solution of ethyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-3-oxo-5(S)-hydroxy-6(E)-heptenoate (Rosuvastatin keto-ester) (2 g, 0.0039 mol) dissolved in a mixture of

tetrahydrofuran (5 ml), methanol (2 ml) and toluene (3 ml) was added at -75°C to -78°C over a period of 5 min followed by sodium borohydride (0.225 g, 0.59 mol) in one lot at -78°C. The reaction mixture was stirred at the above temperature and monitored the progress of the reaction by HPLC till disappearance of the Rosuvastatin keto-ester. The mass was quenched with acetone (3 ml) and acetic acid (3 ml) at -78°C to -75°C. Subsequently, the temperature of the reaction mass was raised to -55°C and diluted with ethyl acetate (40 ml) and water (40 ml). The temperature was further raised to 25-30°C and organic layer was separated. The aqueous layer was reextracted with ethyl acetate (25 ml) and the combined organic layer was washed with aqueous sodium bicarbonate solution (8% w/w, 2 x 40 ml) followed by 25% aqueous sodium chloride (40 ml). The solvent was distilled under reduced pressure (50-100 mm Hg) at 40-45°C to obtain the crude product as an oily mass, which was crystallized from a mixture of ethyl acetate (4 ml), ethanol (2 ml) and n-heptane (16 ml) at 25-30°C. The product obtained was filtered and dried at 35-40°C under vacuum. Yield: 1.7 g Purity: 99.05 % Anti isomer: 0.86 % Rosuvastatin keto-ester: 0.04 %
EXAMPLE-4
PREPARATION OF (+) ETHYL 7-[4-(4-FLUOROPHENYL)-6-
ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)
PYRIMIDIN-5-YL]-(3R,5S)-3,5-DIHYDROXY-6(E)-HEPTENOATE
(ROSUVASTATIN ETHYLESTER)
A mixture of tetrahydrofuran (60 ml), methanol (13 ml) and ethyl acetate (10 ml) was cooled to -78°C under nitrogen atmosphere and diethylmethoxyborane (1.17 ml, 48% w/w in tetrahydrofuran) was added to it dropwise over a period of 10 min at that temperature. Ethyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-

methylsulfonylamino)pyrimidin-5-yl]-3-oxo-5(S)-hydroxy-6(E)-heptenoate (Rosuvastatin keto-ester) (2 g, 0.0039 mol) was dissolved in a mixture of tetrahydrofuran (5 ml), methanol (2 ml) and ethyl acetate (6 ml) and added dropwise to the above reaction mass over a period of 15 min at -75°C to -78°C. Sodium borohydride (0.225 g, 0.0059 mol) was added in one lot at the above temperature. The reaction mass was stirred at -75°C to -78°C till the starting material disappeared as monitored by HPLC in the reaction mass. After completion of the reaction, the product was isolated as per the work-up procedure described in the example (3). Yield: 1.7 g Purity: 99.17% Anti isomer: 0.74 % Rosuvastatin keto-ester: Nil
EXAMPLE-5
PREPARATION OF (+) ETHYL 7.(4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO) PYRIMIDIN-5-YL]-(3R,5S)-3,5-DIHYDROXY-6(E)-HEPTENOATE [ROSUVASTATIN ETHYLESTER]
Diethylmethoxyborane (5 ml, 4 molar solution in tetrahydrofuran) was added to a
cooled mixture of tetrahydrofuran (50 ml), methanol (15 ml) and ethyl acetate (6
ml) at -78°C, Sodium borohydride (0.8 gm) was added to the above reaction mass
in one lot at -78°C and stined for 15 minutes at that temperature before addition
of ethyl-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methyi
sulfonylamino)pyrimidin-5-yl]-3-oxo-(5S)-5-hydroxy-(6E)-heptenoate (3-keto-5-hydroxy-ethyl Rosuvastatin) [2 gm dissolved in a mixture of tetrahydrofuran (5 ml), ethyl acetate (2 ml) and methanol (2 ml)] over a period of 30 min at -75°C to ~78°C. The above reaction mass was stirred for 2 hours for complete disappearance of the starting material (3-keto-5-hydroxy ethyl Rosuvastatin) by HPLC and quenched by adding to a buffer solution of pH : 3 (100 ml). The

organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layer was washed with 2% aqueous sodium bicarbonate (50 ml x 2) followed by aqueous sodium chloride (20% w/w, 50 ml). The solvent was distilled out under reduced pressure at 40-45°C to obtain the product as an oily mass, which was further co-distilled with methanol (50 ml x 3) and finally crystallized from isopropyl acetate (7.2 ml) and n-heptane (18 ml). Yield: 1.53 gm Purity: 98.84% Anti-isomer: 0.88% Rosuvastatin Keto-ester: Nil
EXAMPLE-6
PREPARATION OF (+)-(3R,5S)-7-[4-(4-FLUOROPHENYL)-6-
ISOPROPYL-2-(N-METHYL-N-METHYL SULFONYLAMINO)
PYRIMIDIN-5-YL]-3-5-DIHYDROXY-6(E)- HEPTENOIC ACID
CALCIUM SALT
(3R,5S)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino) -pyrimidin-5-yl]-3,5-dihydroxy-6(E)-heptenoic acid ethyl ester (5 g, 0.0098 ml) was dissolved in a mixture of ethanol and tetrahydrofuran (27.5 ml, ethanol : tetrahydrofuran 5 : 0.5 v/v) at 20°C and cooled to 10°C, Thereafter, IN aqueous sodium hydroxide (9.8 ml) was added drop wise to the above reaction mass and stined at 25-30°C for 4 h. After completion of the reaction, the solvent was distilled under reduced pressure at 35-40°C and the residue obtained was dissolved in a mixture of water (48 ml), ethanol (1,5 ml) and tetrahydroftaran (1 ml) at 25°C. It was further extracted using a mixture of toluene:ethyl acetate (6 : 4 v/v) (12.5 ml X 4) at 25°C. The aqueous layer obtained after extraction was filtered through hyflo and concentrated under reduced pressure (20-40 mm Hg) to a volume of-35 ml at 35-40°C. Aqueous calcium chloride (25 ml) (prepared by dissolving 1.44 g calcium chloride dihydrate in 10 ml of water and making up the volume to 25 ml) was added to the above layer at 25°C over a period of 1 h during

which the product precipitated out. The above suspension was stirred for 3 h at 25-30°C, filtered and washed with water (5x2 ml). Finally, it was dried under reduced pressure (10-20 mm Hg) at 35-40°C till the moisture content was -1.8-2%. Yield: 3.5 g.

WE CLAIM
1) An improved process for preparing Rosuvastatin alkyl ester of Formula II,

wherein R represents straight or branched C1.5 alkyl, aryl, aralkyl which comprises:
a) reducing Rosuvastatin keto ester of Formula III

with a hydride ion source and dialkylalkoxyborane at low temperature in a mixture of three or more organic solvents each selected from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) maintaining the reaction mass at the same temperature under stirring for completion of reaction;
c) isolating the compound of Formula II.
2) An improved process for preparing Rosuvastatin alkyl ester of Formula II,


wherein R represents straight or branched C1-5 alkyl, aryl, aralkyl which comprises:
a) combining Rosuvastatin keto ester of Formula III

with dialkylalkoxyborane at low temperature in a mixture of three or more organic solvents selected each from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) adding hydride ion source at temperature ranging from -50°C to -90°C to step (a) mixture;
c) maintaining the reaction mass at the same temperature under stirring for completion of reaction;
d) quenching the reaction mass with water or acids such as acetic acid, trifluoroacetic acid or bases like aqueous sodium bicarbonate, aqueous potassium carbonate or peroxide like aqueous hydrogen peroxide and the like to obtain compound of Formula II.
3) An improved process for preparing Rosuvastatin alkyl ester of Formula II,


wherein R represents straight or branched C1-5 alkyl, aryl, aralkyl which comprises:
a) combining dialkylalkoxyborane, hydride ion source at low temperature in a mixture of three or more organic solvents selected each from an ethereal solvent, alcoholic solvent and an aprotic solvent;
b) adding a solution of Rosuvastatin keto ester of Formula III

to step (a) mixture;
c) maintaining the reaction mass at the same temperature under stirring for completion of reaction;
d) quenching the reaction mass with water or acids such as acetic acid, trifluoroacetic acid or bases like aqueous sodium bicarbonate, aqueous potassium carbonate or peroxide like aqueous hydrogen peroxide and the like to obtain compound of Formula II.
4) The process according to claims 1, 2 and 3 in step (a), wherein the organic solvent used is selected from the group consisting of an ethereal solvent selected from C2-C8 ethers or cyclic ethers such as diethyl ether, dimethyl ether, tetrahydrofuran; alcoholic solvent selected from C1-C4 alcohol such as methanol, ethanol, butanol and aprotic solvents such as toluene, alkyl esters

such as ethyl acetate, methyl acetate, chlorinated solvents such as methylene chloride, chloroform.
5) The process according to claim 4, wherein the preferred mixture of solvents is tetrahydrofuran, methanol and ethyl acetate or tetrahydrofuran, methanol and toluene.
6) The process according to claim 1 step (a), claim 2 step (b) and claim 3 step (a), wherein the source of hydride ion is selected from the group consisting of sodium borohydride, potassium borohydride, lithium borohydride and sodium triacetoxy borohydride.
7) The process according to claim 6, the source of hydride ion is present in an amount of 1 to about 4 equivalent (per gram of Rosuvastatin keto ester of Formula III).
8) The process according to claim 6, addition of hydride ion temperature is in the range of-50°C to-95°C.
9) The process according to claims 1, 2 and 3, wherein the dialkylalkoxyborane is selected from diethylmethoxyborane, dimethylmethoxyborane, diethylethoxyborane, dimethylethoxyborane.
10) The process according to claim 9, the dialkylalkoxyborane is used in the range of 1-10 m. eq. based on Rosuvastatin keto ester of Formula III.
11) The process according to claims 1, 2 and 3, wherein the total volume of solvent mixture used during the reduction step is about 10 volumes to 80 volumes (ml per gram of Rosuvastatin keto ester of Formula III).

12) The process according to claim 11, total volume of solvent mixture is preferably 30-40 volumes.
13) The process according to claims 1, 2 and 3, wherein the Rosuvastatin alkyl ester of Formula II is further recrystallized to obtain pure Rosuvastatin alkyl ester of Formula II
14) The process according to claim 13, the process comprises:
a) preparing a solution of Rosuvastatin alkyl ester of Formula II, in an organic solvent selected from C1-C5 alcohol such as methanol, ethanol, butanol; C3-C8 esters such as ethyl acetate, methyl acetate; C3-C8 ketones such as methylethyl ketone, methylisobutyl ketone, acetone; C6-C10 aromatic hydrocarbons such as toluene; ethers such as tetrahydrofuran, methylethyl ether; acetonitrile and mixture thereof and cooling the mass to give Rosuvastatin alkyl ester of Formula II.
15) The process according to claim 13, the process comprises:
a) preparing a solution of Rosuvastatin alkyl ester of Formula II, in an organic solvent selected from C1-C5 alcohol such as methanol, ethanol, butanol; C3-C8 esters such as ethyl acetate, methyl acetate; C3-C8 ketones such as methylethyl ketone, methylisobutyl ketone, acetone; C6-C10 aromatic hydrocarbons such as toluene; ethers such as tetrahydrofuran, methylethyl ether; acetonitrile and mixture thereof;
b) treating the above solution from step (a) with an anti solvent like aliphatic hydrocarbons like, pentane, hexane, heptane, cyclohexane and the like;
c) stirring the resulting slurry from step (b) for 1 h to 48 h to give pure Rosuvastatin alkyl ester;
d) collecting the resulting pure Rosuvastatin alkyl ester.

16) The process according to claims 1, 2, 3 and 11, the Rosuvastatin alkyl ester of Formula II is further converted to Rosuvastatin calcium, with high purity.