[ CAS No. 355806-00-7 ] {[proInfo.proName]}

Name: 355806-00-7|(3R,5S,6E)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-[(methanesulfonyl) methylamino]pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid tert-butyl ester|97%
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Quality Control of [ 355806-00-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 355806-00-7 ]

Product Details of [ 355806-00-7 ]

CAS No. :	355806-00-7	MDL No. :	MFCD08460212
Formula :	C₂₆H₃₆FN₃O₆S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IJHZGLLGELSZAF-OKLSWEBGSA-N
M.W :	537.64	Pubchem ID :	11478210
Synonyms :

Calculated chemistry of [ 355806-00-7 ]

Physicochemical Properties

Num. heavy atoms :	37
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.5
Num. rotatable bonds :	12
Num. H-bond acceptors :	9.0
Num. H-bond donors :	2.0
Molar Refractivity :	142.18
TPSA :	138.3 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-7.49 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.83
Log Po/w (XLOGP3) :	2.95
Log Po/w (WLOGP) :	5.05
Log Po/w (MLOGP) :	1.77
Log Po/w (SILICOS-IT) :	4.03
Consensus Log Po/w :	3.53

Druglikeness

Lipinski :	1.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-4.48
Solubility :	0.0178 mg/ml ; 0.0000331 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.52
Solubility :	0.00164 mg/ml ; 0.00000304 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.83
Solubility :	0.000792 mg/ml ; 0.00000147 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	5.1

Safety of [ 355806-00-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 355806-00-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 355806-00-7 ]

[ 355806-00-7 ] Synthesis Path-Downstream 1~88

1
[ 355806-00-7 ]
crestor [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.5%		In 1000 ml by adding reaction bottle 100g compound F, 500 ml of methanol, 100 ml water, 7.5% liquid alkali 11g, in 0-10 C lower stirring for 5 hours, after the reaction, by adding 1M adjusted is neutral PH dilute hydrochloric acid, concentrated under reduced pressure to remove the methanol, the addition of 500 ml water dissolved, add 150 ml methyl tert-butyl ether, stir at room temperature 30 minutes, layering, taking, decompression concentrating 15 minutes, cooling to 10-15C, adding drops of 10% calcium chloride solution of 120g, precipitating a large amount of white solid, filter, vacuum dried to obtain the rosuvastatin calcium 81g, chemical purity 99.6%, optical purity 99.9%, yield 83.5%.
38%		To an aqueous solution of tert-butyl amine salt of rosuvastatin (XVI) (25 g in 125 mL of water), a solution of sodium hydroxide (1.98 g) in water (50 mL) was added under nitrogen atmosphere and the reaction mixture was stirred for 1 hour. The reaction mass was heated to 40-45 C and nitrogen gas was bubbled through the reaction mass under vacuum for 1-2 hrs and water (50 mL)was added to the reaction mass. The reaction mixture was then filtered through 0.2-0.4 micron filter and cooled to 15-20 C. An aqueous solution of calcium chloride (2.75 g in 75 mL water) was added slowly to the reaction mixture for a period of 15-25 minutes and the reaction mixture was stirred for 15-45 minutes. The precipitated solid was filtered and washed with water. The wet cake was dried in vacuum oven below 50 C for 6-10 hours. The dried material was sieved and charged into a reaction vessel and water (300 mL) was added to it. The reaction mixture was stirred for 15-45 minutes at 25-35 C under nitrogen atmosphere. The solid was filtered and dried to provide the title compound.Yield: 17.4 g (38 %)Purity by HPLC: 99.77 %.
		Example 7- (Preparation in ACN/H20) A 250ML flask equipped with a mechanical stirrer was charged with ACN (25 mL), t- Butyl-Rosuvastatin (5 g), H20 (25 mL) and NAOH pellets (1. 86G). The mixture was stirred at ambient temperature for 2 hours. The phases were separated in a separating funnel. The aqueous phase was concentrated under reduced pressure to obtain an oily residue (12.0 g). To this residue was added water (40 ml) and 5.5 g CaCl2. The solution was stirred at ambient temperature for 15 hours (overnight) to form a white precipitate. The organic phase was concentrated under reduced pressure to obtain an oily residue (13.0 g). To this residue were added 40 mL water and 5.5 g CaCl2. The solution was stirred at ambient temperature for 15 hours (over night) to FORM a white precipitate. Both parts were filtered and washed with 10 mL of water to get a powdery compound. (0. 86 g from aqueous phase, 4.01 g from organic phase)

		Example 8- (Preparation in Toluene/H20) A 250ML flask equipped with a mechanical stirrer was charged with toluene (25 mL), 5 g t-Butyl-Rosuvastatin, 25 mL H20, 0.75 g of TBAB (tetrabutylammonium bromide) (15% W/W) and 1. 86 g NAOH pellets. The mixture was stirred at ambient temperature for 2 hours. The phases were separated in an apparatus funnel. Traces of toluene in the aqueous phase were distilled off under reduced pressure at 40C to obtain a thick slurry (36.0 g). To this slurry was added 49.5 g CaCl2 1N dropwise. The solution was stirred at ambient temperature for 1.5 hours, filtered and washed with 10 mL of water to get a powdery compound.; Example 10- (preparation in Toluene/H20, 5EQ NAOH)) A 250ML flask equipped with a mechanical stirrer was charged with toluene (25 mL), 5 g t-Butyl-Rosuvastatin, 25 mL H2O, 0.75 g TBAB (tetrabutylammonium bromide) (15% w/w) and 1.86 g NAOH pellets. The mixture was stirred at ambient temperature for 2 hours. The phases were separated in a separation funnel. Traces of toluene in the aqueous phase were distilled off under reduced pressure at 40C to obtain a slurry (24.0 g). Make-up of water was done (26 mL) at the end of the evaporation to obtain a clear solution. To this solution was added 3.3 g CaCl2 IN L0 ML water dropwise. The solution was stirred at ambient temperature for 2 hours, filtered and washed with LOML of water to get a powdery compound.
		EXAMPLE 9- (PREPARATION IN CHLOROBENZENE (MCB) /H20) A 250ML flask equipped with a mechanical stirrer was charged with chlorobenzene (50 ML), 5g t-Butyl-Rosuvastatin, 50 mL H20, 0.75 g TBAB (tetrabutylammonium bromide) (15% w/w) and 1.12g NAOH pellets. The mixture was stirred at ambient temperature for 8 hours. The phases were separated in an separating funnel. Traces OF MCB IN the aqueous phase were distilled off under reduced pressure at 40C to obtain a slurry (24.0 g). Make-up of water was done (26 mL) at the end of the evaporation to obtain a clear solution. To this solution was added 3.3 g CaCl2 in 10 mL water dropwise. The solution was stirred at ambient temperature for 2 hours, filtered and washed with 10 mL of water to get a powdery compound.
		Example 10; Preparation of calcium (2:l)-(+)7-{4-(4-flurophenyl)-6-isopropyl-2- [methyl(methylsulfonyl)amino]pyrimidin-5-yl}(3R,5S)-3,5-dihydroxy-(E)-hept-6-enoic acidA solution of tert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2-[methyl(methyl sulfonyl)amino]pyrimidin-5-yl}'(3R,5S)-3,5-dihydroxyhept-6-enoate (2g; 3.72mmol) in 30ml of acetonitrile of 0.25 M solution of NaOH (14.9ml; 3.72mmol) was added over a period of 5 minutes at temperature between 26 -290C with stirring. After stirred for 3-4 hours, 30ml of tert-butyl methyl ether was added followed by 10ml of water. The layers were separated and the organic layer was extracted with 20ml of water. The combined aqueous layers were concentrated by evaporation under reduced pressure to its half volume. To the concentrated aqueous layer, 1 M solution of CaCl2.2H2O (1.86ml; 1.86 mmol) was added dropwise with stirring at 25 - 280C. After stirred for 45 minutes, the EPO <DP n="18"/>precipitate formed was filtered and washed with water to obtain Rosuvastatin calcium as a white solid. EPO <DP n="19"/>
		Example-2:40 g of Rosuvastatin diol ester as prepared in example-1 above was taken in 400 mL of methanol at 25C to 35nC and cooled to 20"-25"C. The mixture of sodium hydroxide (3.6 g) and water (72 mL) solution was added to above solution within 30 minutes. After complete addition, the solution was stirred and further cooled to 10- 200C. The pH was adjusted between 7.5-8.5 by IN HCl (17 mL). Remaining mixture was washed with toluene at 20 to 300C. The aqueous layer was subjected to distillation <n="11"/>under vacuum to remove MeOH below 500C till remaining volume becomes 130 mL. The volume was adjusted to 250 mL by adding water. The remaining mixture was passed through hydrobed and washed with water. A solution of 10.3 g calcium chloride in 40 mL water was added to the reaction mixture and the solution was filtered at 150C to 200C. The temperature was raised upto 250C to 35C and stirred for 1 hr. The product was filtered and washed with water. The product was dried at 500C to 55C to get 34.7 g of Rosuvastatin Calcium having individual impurity less than 0.1% HPLC Purity > 99.65% .
		Example 17(E)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5- yl](3i?,5)S)-3,5-dihydroxyhept-6-enoic acid, hemi-calcium salt I;Tetrahydrofuran (35 ml) is added to weighed tert-butyl ester XII (5 g). 40% solution of LiOH (10 ml) is added to the solution over 5 minutes, and the heterogenous mixture is stirred vigorously for 3 hours and then poured into a separatory funnel containing demineralized water (150 ml) and hexane (50 ml). After complete separation, ethyl acetate (40 ml) is poured into the aqueous phase and calcium acetate (2 g) is added. After 10 minutes of vigorous stirring, the phases are separated, and the aqueous phase is reextracted with ethyl acetate (20 ml). The ethyl acetate extract is washed with demineralized water (2 x 5 ml), dried, and evaporated, and the evaporation residue is dissolved in acetone and sprayed into the stream of an inert gas. 4.5 g of amorphous rosuvastatin is obtained.HPLC: 99.2 %.
	With calcium acetate; In water; at 20℃; for 2.78333h;	The mixture was then extracted with toluene (3000 mL) and stirred at RT for half an hour. An aqueous phase formed and was isolated. The aqueous phase was concentrated under reduced pressure at 40 C. to half of the volume. Half of the remaining aqueous phase was transferred to a 500 mL reactor and water (110 mL) was added, creating a solution. The solution was stirred at RT for 5 minutes. Ca(OAc) (8.8 g) was added dropwise to t he solution over 117 min. at RT. The solution was stirred at RT for 1 hour, filtered, and washed with 60 mL of water, yielding a powdery compound (26 g, 94%).
		A solution of tert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2-[methyl(methyl sulfonyl)amino]pyrimidin-5-yl}(3R,5S)-3,5-dihydroxyhept-6-enoate (2g; 3.72 mmol) in 30ml of acetonitrile of 0.25 M solution of NaOH (14.9ml; 3.72 mmol) was added over a period of 5 minutes at temperature between 26 -290C with stirring. After stirred for 3-4 hours, 30 ml of tert-butyl methyl ether was added followed by 10ml of water. The layers were separated and the organic layer was extracted with 20ml of water. The combined aqueous layers were concentrated by evaporation under reduced pressure to its EPO <DP n="22"/>half volume. To the concentrated aqueous layer, 1 M solution of ( 1.86ml: 1.86 mmol) was added drop wise with stirring at 25 - 28T. After stirred for 45 minutes, the precipitate formed was filtered and washed with water to get Rosuvastatin Calcium as a white solid.
		Example 14Rosuvastatin calcium60,0 g rosuvastatin t-butyl ester (Compound of Example 13) and 21 ,0 ml 8M NaOH in 120 ml THF and 300 ml demi water are stirred at 500C for 2 hours whereupon the mixture is cooled to room temperature and washed twice with 540 ml of methylcyclohexane. Aqueous phase is evaporated at 600C under reduced pressure to 220 ml of total volume to eliminate organic solvents. The residue is rediluted with degassed demi-water to 440 ml of total volume. To the resulting solution 1 ,0 g of charcoal is added and the suspension is stirred half an hour. Aqueous solution of calcium chloride is added to the filtrate during stirring on ice-bath. The suspension formed is treated vigorously with ultraturrax at cca 18000 rpm for 3 minutes. The precipitate is filtered off, suspended in 100 ml demi water and treated again with ultraturrax at 18000 rpm for 3 minutes on ice-bath. The product is separated by filtration, washed with 30 ml ice-cold degased demi-water, collected from the filter and dried 12 hours at 500C in vacuum desiccator. Yield: 25,05 g of rosuvastatin calcium (99,75% area, HPLC)
18 g		EXAMPLE-8PREPARATION OF (3R,5S,6E) 7- [4-(4-FLUOROPHENYL)-6-ISOPROPYL-2- (NMETHYL(N-METHYLSULFONYL)AMINO]PY IUMIDIN-5-YL]-3,5-DIHYDROXY-6.-HEPTENOIC ACID, CALCIUM SALT [ROSUVASTAT1N CALCIUM]Rosuvastatin tert-butyl ester (20 g, 0.03 7 mole) was dissolved in a mixture of ethanol (100 ml) and tetrahydrofuran (20 ml) at 20-30C. It was cooled to 0-5C and added an aqueous solution of sodium hydroxide (1.53 g, Assay 97%, dissolved in 15 ml of water) slowly over a period of 30 mm. Thereafter, temperature of the reaction mass was raised to 20-30C. The progress of the reaction was monitored by HPLC. After completion of the reaction, pH of the reaction mass was adjusted to 10 with dilute HC1 and solvents were evaporated under reduced pressure. Water (200 ml) was added to it and extracted with methyl tert-butyl ether (50). Traces of solvents were evaporated from the aqueous layer and aqueous calcium chloride was added at 20-25C. The precipitated product was isolated by filtration and dried under reduced pressure at 30-40C to obtain title compound. Yield: 18 gChromatographic Purity (by HPLC): 99.9%. Anti-isomer: 0.09%
4.3 g		50 mL of acetonitrile was added to the reactor, and 50 mL of acetonitrile was added to the solution of tert -butyl (3R, 5S, 6E) 7 [4 (4 fluorophenyl) 6 isopropyl 2 (N methylmethylsulfonamido) pyrimidine 5 6.0 g of diethyl 3,5-dihydroxyhept-6-enoate is dissolved in the solution. After maintaining the temperature of the reaction solution at 28 to 33 C, 12.8 ml of a 2N aqueous sodium hydroxide solution was added dropwise at 28 to 33 C for 10 minutes. When the addition was completed, the reaction was continued at 28 to 33 C for 3.5 hours. After completion of the reaction, 80 mL of water and 50 mL of ethyl acetate are added to the reactor, and the mixture is stirred at 28 to 33 C for 30 minutes. After the reaction solution is purified and separated, the aqueous solution layer is filtered to remove insolubles. A solution prepared by dissolving 1.13 gr of calcium acetate monohydrate in 20 mL of water was added dropwise to the aqueous solution layer for 20 minutes, followed by stirring for 20 hours. The crystals formed were filtered, washed with water and then vacuumed at an internal temperature of 50 to 55 C to obtain 4.3 g of the title compound.

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2
[ 355806-00-7 ]
rosuvastatin sodium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide; water; In tetrahydrofuran; at 30 - 50℃; for 1 - 2h;Product distribution / selectivity;	Example 1; Preparation of rosuvastatin calcium salt via rosuvastatin sodium salt solution; Rosuvastatin te/f-butyl ester (60.0 g, 111.6 mmol) is dissolved in 500 mL of a 4:1 mixture of THF / water. The clear solution is warmed to 30 0C and 8.0 M NaOH (15 mL, 120.0 mmol) is added portionwise. The reaction mixture is stirred at 30 X for 2 hours giving a clear yellow solution. Then THF is removed completely under the reduced pressure (20 mbar) at 40 0C. The remaining aqueous solution is diluted with water to 500 mL and washed with AcOEt (2*200 mL). After separation from the organic layer aqueous phase is distilled under the reduced pressure (20 mbar) at 40 0C to completely remove the dissolved AcOEt. The remaining clear solution of sodium rosuvastatinate (440 mL) is diluted with water (60 mL) to 500 mL and warmed to 40 0C. To a vigorously stirring solution of sodium rosuvastatinate is added dropwise Ca(OAc)2chiH2theta (14.8 g, 84.0 mmol in 60 mL of water) over 5 minutes at 40 0C to precipitate rosuvastatin calcium. After the complete addition the suspension is stirred further for 30 minutes at 40 0C. The white precipitate is filtered off. Then a wet white solid is suspended in water (200 mL) and vigorously stirred for 1 hour at 20 0C. The undissolved precipitate is collected by filtration, washed with water (200 mL) and dried in vacuum at 40 0C to give 48.5 g (86.8 %) of rosuvastatin calcium salt as white powder (HPLC: 99.87 %).; Example 2; Rosuvastatin terf-butyl ester (60.0 g, 111.6 mmol) is dissolved in 120 mL of tetrahydrofuran (THF) and 300 ml of water treated 8.0 M NaOH (21 mL) is added portionwise. The reaction mixture is stirred at 5O0C for 2 hours. Reaction mixture is allowed to cool to room temperature and washed with 2 x 540 ml of methylcyclohexane. EPO <DP n="14"/>Aqueous phase is evaporated at 600C under reduced pressure to 220 ml of total volume to eliminate organic solvents. The residue obtained is rediluted with degassed demi-water to 440 ml of total volume. To the resulting solution 1.0 g of charcoal is added and the suspension is stirred half an hour. Charcoal is filtered off. One half of the volume of the filtrate (220 ml of total 440 ml) 25.5 ml aqueous solution of calcium chloride (prepared from 10.5 ml 4M calcium chloride and 15 ml demi- water) is added during stirring on ice-bath. The suspension formed is treated vigorously with ultraturrax at cca 18000 rpm for 3 minutes. The precipitate is filtered off, suspended anew in 100 ml demi water and treated again with Ultraturax at 18000 rpm for 3 minutes on ice-bath. The product is separated by filtration, washed with 30 ml ice-cold degassed demi-water, collected from the filter and dried 12 hours at 500C in vacuum desiccator.Yield: 25.05 g of amorphous rosuvastatin calcium (99.75% area, HPLC, 0.085 % Na)The second aliquot of 220 ml of filtrate is treated on the same way except mechanical stirring instead of ultraturax mixing is performed. Yield 25.11 g (99.72% area, HPLC, 1.55 % Na); Example 3; Rosuvastatin fe/f-butyl ester (10.0 g) is dissolved in 20 mL of tetrahydrofuran and 50 ml of water treated 8.0 M NaOH (3.51 mL) is added portionwise. The reaction mixture is stirred at 500C for 1 hours. One third (26 ml of the total 78 ml) of the resulting solution is washed with 35 ml methylcyclohexane. Methylcyclohexane phase is extracted with 3 ml demi water. Combined aqueous phases are washed with 20 ml /so-propyl acetate. Aqueous phase is then concentrated by evaporation under reduced pressure at 50C to 15 - 20 ml of total volume. It is cooled on ice-bath and gradually 1.1 ml aqueous solution of 4M calcium chloride is added within a minute during stirring. It is stirred additional 30 minutes on ice-bath and the precipitated product is separated by filtration. The precipitate is washed with 4.0 ml demi water, EPO <DP n="15"/>collected from the filter and dried at room temperature 12 hours in vacuum desiccator.Yield: 2.22 g of amorphous rosuvastatin calcium.Two further aliquots are washed with 20 ml ethyl acetate or 20 ml terf-butyl methyl ether respectively with similar yield and quality.; Example 4; Preparation of rosuvastatin sodium salt; Rosuvastatin fe/-butyl ester (3.0 g, 5.6 mmol) is dissolved in 25 mL of a 4:1 mixture of THF / water. The clear solution is warmed to 30 0C and 8.0 M NaOH (0.75 mL, 6.0 mmol) was added portionwise. The reaction mixture is stirred at 30 0C for 2 hours giving a clear yellow solution. Then THF is removed completely under the reduced pressure (20 mbar) at 40 0C. The remaining aqueous solution is diluted with water to 25 mL and washed with AcOEt (2x10 mL). After separation from the organic layer aqueous phase is distilled under the reduced pressure (20 mbar) at 40 0C to completely remove the dissolved AcOEt. The remaining clear solution of sodium rosuvastatinate is diluted with water to 25 mL and liophylized to afford 2.81 g (100 %) of rosuvastatin sodium salt as white powder.; Example 8; Preparation of solid rosuva...
97%	With water; sodium hydroxide; In acetonitrile; at 20℃; for 7h;	(2) Preparation of sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl) amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV) To a 5 L four-necked flask, 2 L (10 mL/g) of acetonitrile and 200 g (1 mol) of tert-butyl 6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methanesulfonyl)amino]-5-pyrimidinyl]vinyl]-2,2-dimethyl-1,3-dioxane-4-acetate (compound III) were added, and stirred to homogeneity, followed by adding 14.8 g (0.02 mol, calculated from titrated content) of an aqueous solution of hydrochloric acid having a mass percentage concentration of 0.06%. The system was warmed up to 35 C. and stirred at the same temperature for 5 hours until compound III was completely consumed. To the reaction system was added dropwise 32.5 g (1.1 mol) of an aqueous solution of sodium hydroxide having a mass percentage concentration of 4%, and stirred at 20 C. for 7 hours until the dihydroxy ester intermediate produced in the first phase was completely consumed. The system was concentrated to remove acetonitrile, followed by adding 2 L (10 mL/g) of purified water, and stirred to clearness. The system was extracted three times with 400 mL (2 mL/g) of methyl tert-butyl ether. The aqueous phase was further concentrated until no organic solvent was left, to give the an aqueous solution of the product, sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV), with a purity of >98% and a yield of 97%.
92%	With sodium hydroxide; In ethanol; at 0 - 20℃; for 1h;	A solution of the compound of formula (41) (4.2 g, 7.8 MMOL) in ethanol (100 ML) IS added dropwise, at 0C, to a solution of sodium hydroxide (0. 1 M in water, 76 ml). The ice bath is removed and the reaction mixture is stirred at room temperature for 1 hour. The solvent is then drawn off using a rotary evaporator and the crude product is made to crystallise by adding ether. In that manner, 3.6 G (92 %) of the sodium salt (42) can be obtained in the form of a slightly yellowish powder. 1H NMR (300 MHz, D20): 1.14 (d, J = 6.7 Hz, 6H); 1.39-1. 42 (m, 1H) ; 1.50-1. 61 (m, 1H) ; 2.10-2. 24 (m, 2H); 3.21-3. 38 (m, 1H) ; 3.36 (s, 3H); 3.46 (s, 3H); 3.61-3. 72 (m, 1H) ; 4. 18-4. 24 (m, 1 H) ; 5.39 (dd, J = 8.5, 8.5 Hz, 2H); 7.40-7. 49 (m, 2H).

91%		7 g (14.5 mmol) of 7-[4-(4-fluorophenyl)-6-isopropyl-2- (methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3i-,5iS)-dihydroxy- hept-6-enoic acid tert-butylester are stirred until complete dissolution in 200 ml of ethanol and at room temperature in 20 minutes 58 ml of 0.25 M sodium hydroxide solution (14.5 mmol) are added dropwise. <n="25"/>The mixture is reacted for 4 hours at the temperature of 60 0C, the solution is filtered through a G4 sintered glass filter and the ethanol is evaporated at the pressure of 20 Hgmm. The residue is diluted with 40 ml of water and extracted three times with 15 ml of ethylacetate each, the aqueous layer is evaporated at the pressure of 20 Hgmm. From the residue, 2x10 ml of ethanol is evaporated and the solids thus obtained are stirred in 40 ml of diisopropyl-ether and filtered.Yield, 6.65 g (91 %).The product is identical in all respects with that obtained inExample 2.
89.7%		2.35 g of the obtained 1,3-syn-diol compound was added to a 100 mL round flask equipped with a stirrer and a thermometer, 10 mL of formic acid was added thereto, and the mixture was stirred at room temperature. The progress of the reaction was confirmed by TLC (Thin Layer Chromatography; Eluent: dichloromethane / methanol, 4/1). After the reaction was completed, the reaction mixture was concentrated, 40 mL of ethanol and 50 mL of 0.1 N sodium hydroxide were added thereto, followed by stirring at room temperature for 10 minutes.After the reaction was concentrated, 20 mL of ethanol was added and stirred for 10 minutes and then concentrated. Then,50 mL of ether was added to the dispersion, followed by stirring at room temperature for 1 hour. The white crystals thus produced were collected on a filter paper, Washed with 10 mL of ether three times, and dried to obtain rosuvastatin sodium salt in a yield of 89.7%.
	With sodium hydroxide; ethanol; water; at 20℃; for 1 - 2h;	Example 1 A 250ML flask equipped with a mechanical stirrer was charged with ETOH (100 mL) and t-Butyl-rosuvastatin Example 1 A 250ML flask equipped with a mechanical stirrer was charged with ETOH (100 mL) and t-Butyl-rosuvastatin (10 g). To the suspension, NAOH 1N 1. 5eq (27.93 mL) was added portionwise at ambient temperature. The mixture was stirred at ambient temperature for one hour. After 1 hour, the resulting clear solution was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present in the solution. [HPLC sample at the end of reaction]. Then the reaction mixture was concentrated under reduced pressure at 60C to obtain a residue (17.79gr) that contained the sodium salt. [HPLC sample after evaporation]. To this residue was added 100 mL water and the solutions was stirred at ambient temperature for 5 minutes. The aqueous phase was washed with EtOAc (3xlOOmL). [HPLC sample of aqueous phase and sample of the organic phase]. Traces of EtOAc in the aqueous phase were distilled off under reduced pressure at 60C. Make-up of water was done (35 mL-40 mL) at the end of the evaporation. To this solution CaCl2 1N (20 mL) was added dropwise over 10 minutes at ambient temperature resulting in precipitation of the calcium salt. The reaction mixture was then stirred at 15C for 2 hours, filtered and washed with 10 mL of water to get a powdery compound (8.0 g, 86 %). [HPLC dry Ca-salt, HPLC ML of Ca-salt].; Example 2 A 250ML flask equipped with a mechanical stirrer was charged with ETOH (50ML) and t- butyl-rosuvastatin (5 g). To the suspension, NAOH 1N 1.5 eq. (13.5 mL) was added portionwise at ambient temperature. The mixture was stirred at ambient temperature for one hour. After 1 hour, the clear solution was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present in the solution. Then the reaction mixture was concentrated under reduced pressure at 60C to obtain a residue that contained Na-salt. To this residue was added 50 mL water, and the solution was stirred at ambient temperature for 5 minutes. The aqueous phase was washed with methyl ethyl ketone ("MEK") (3X50ML). Traces OF MEK in the aqueous phase were distilled off under reduced pressure at 60C. Make-up of water was done (15 mL-20 mL) at the end of the evaporation. To this solution CaCl2 1N (10 mL) was added dropwise over 10 minutes at ambient temperature to precipitate the calcium salt. The reaction mixture was then stirred at 15C for 2LORS, filtered and washed with water to get s powdery compound (2.3g, 50%).; Example 3 A 100ML flask equipped with a mechanical stirrer was charged with ETOH (50 mL) and t- butyl-rosuvastatin (5 g). To the suspension, NAOH 1N 1.5 eq. (13.96 mL) was added portionwise at ambient temperature. The mixture was stirred at ambient temperature for one hour. After 1 hour, the clear solution was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present in the solution. Then the reaction mixture was concentrated under reduced pressure at 40C to obtain a residue (10.0 g) that contained Na-salt. To this residue was added 45-50 mL water and the solution was stirred at ambient temperature for 5 minutes. The aqueous phase was washed with Toluene (3x25mL). The solution was filtered under reduced pressure with Synter and Carbon after the first extraction. Traces of toluene in the aqueous phase were distilled off under reduced pressure at 400C. Make-up of water was done (25 mL-30 mL) at the end of the evaporation. To this solution CaCl2 1N (10 ML) was added dropwise over 10 minutes at ambient temperature to precipitate rosuvastatin calcium. The reaction mixture was then stirred at ambient temperature for 2 hours, filtered and washed with 10 mL of water to get a powdery compound (3.8g, 81.6%).; Example 4 A 100ML flask equipped with a mechanical stirrer was charged with ETOH (50 mL) and t- butyl-rosuvastatin (5 g). To the suspension, NAOH 1N 1.5 equivalents (13.96 mL) was added portionwise at ambient temperature. The mixture was stirred at ambient temperature for one hour. After 1 hour, the clear solution was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present in the solution. Then the reaction mixture was concentrated under reduced pressure at 40C to obtain a residue (10.0 g) that contained Na-salt. To this residue was added 45-50 mL water and the solution was stirred at ambient temperature for 5 minutes. The aqueous phase was washed with di-ethyl carbonate ("DEC") (3x25mL). Traces of DEC in the aqueous phase were distilled off under reduced pressure at 40C. Make-up of water was done (25 mL- 30 mL) at the end of the evaporation. To this solution, CaCl2 IN (10 mL) was added dropwise over 10 minutes at ambient temperature to precipitate rosuvastatin calcium. The reaction mixture was then stirred at ambient temperature for 2 hours, filtered and washed with 10 mL of water to get a powdery compound ...
	With sodium hydroxide; water; In N,N-dimethyl acetamide; at 20℃; for 0.5h;Product distribution / selectivity;	Example 5; Rosuvastatin te/f-butyl ester (3.0 g, 5.6 mmol) is dissolved in Lambda/,Lambda/-dimethylacetamide (4 mL) at ambient temperature giving a clear yellow solution. Then NaOH 8.0 M (0.75 mL, 6.0 mmol) is added dropwise to a stirred solution at ambient temperature. The reaction mixture is stirred at ambient temperature for 30 minutes giving a clear yellow solution. Then Et2O (50 mL) is added portionwise to the vigorously stirred reaction mixture which becomes immediately turbid and light yellow oil separated from the mixture. After 20 minutes of vigorous stirring oil solidified and fine white precipitate is EPO <DP n="16"/>formed. The suspension is stirred at ambient temperature for 2.5 hours. The white precipitate (sodium rosuvastatinate) is filtered off and washed with Et2O (2*20 ml_).
	With sodium hydroxide; ethanol; water; at 25℃; for 2h;Product distribution / selectivity;	Example 1: Feeding of CaCh during 1-2 hours; A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (200 niL), water (120 ml), and t-Butyl-Rosuvastatin (40 g), forming a suspension. To this suspension, NaOH 47 % 1.2eq (7.6 g) was added dropwise at 25 +/- 5C. Water (280 ml) was added, forming a mixture. The mixture was then washed with Toluene (200 ml) and stirred at 25 +/- 5C for half an hour, creating an aqueous layer.The aqueous layer was isolated, active carbon was added, stirred at 25 +/- 50C for 30 min. and then filtered under reduced pressure with Sinter. Thereafter this solution was concentrated under reduced pressure at 4O0C to half the solution volume. Make-up of the solution was performed to 10 volumes of water versus TBRE (t-butyl rosuvastatin ester). The solution was then heated to 40-450C. CaCl2 (4.1 g) was added portionwise to this solution over 1-2 hour at 38-45C, forming a suspension. The suspension was then cooled to 25 +/- 5C, stirred at 25 +/- 5C for lhr, filtered and washed with water (3x20 ml) to get a powdery compound (17 g dry, 92%, Chloride content 0.1% by weight).; Example 2: Feeding of CaCh during 5 min; A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (200 mL), water (120 ml), and t-Butyl-Rosuvastatin (40 g), forming a suspension. To this suspension, NaOH 47 % 1.2eq (7.6 g) was added dropwise at 25 +/- 5C, forming a mixture. The mixture was stirred at 25 +/- 5C for two hours. Active carbon was added and the mixture was stirred at 25 +/- 5C for 30 min. Water (280 ml) was then added. The mixture was then washed with Toluene (200 ml) and stirred at 25 +/- 5C for half an hour. EPO <DP n="16"/>The aqueous layer was isolated. Thereafter the solution (i.e., the aqueous layer) was concentrated under reduced pressure at 40C to half the solution volume. Make-up of the solution was performed to 10 volumes of water versus TBRE. The solution was heated to 40- 45C. CaCl2 (4.1 g) was added portionwise to this solution over 5 min at 38-45C, forming a suspension. The suspension was then cooled to 25 +/- 5C, stirred at 25 +/- 5C for lhr, filtered and washed with water (3x20 ml) to get a powdery compound (16.4 g dry, 88%, Chloride content 0.1 % by weight).; Example 3: Feeding with CaCh solid; A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (200 mL), water (120 ml), and t-Butyl-Rosuvastatin (40 g), forming a suspension. To this suspension, NaOH 47% 1.2eq (7.6 g) was added dropwise at 25 +/- 5C. Water (280 ml) was added, forming a mixture. The mixture was then washed with Toluene (200 ml) and stirred ai 25 +/- 5C for half an hour. The aqueous layer was isolated. To this solution (i.e., the aqueous layer) active carbon was added, the solution was stirred at 25 +/- 5C for 30 min. and then filtered under reduced pressure with Sinter. Thereafter the solution was concentrated under reduced pressure at 4O0C to half the solution volume. Make-up of the solution was performed to 10 volumes of water versus TBRE. The solution was heated to 40-45 C. CaCl2 (4.1 g) was added to this solution over 1-2 hours at 38-45C, forming a suspension. The suspension was then cooled to 25 +/- 5C, stirred at 25 +/- 5C for lhr, filtered and washed with water (3><20 ml) to get a powdery compound (17 g dry, 92 %, Chloride content 0.1 % by weight).; Example 4: Feeding with a solution of CaCIg; 2N A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (200 mL), water (120 ml), and t-Butyl-Rosuvastatin (40 g), forming a suspension. To this suspension, NaOH 47 % 1.2eq (7.6 g) was added dropwise at 25 +/- 5C, forming a mixture. The mixture was stirred at 25 +/- 5C for two hours. To this mixture active carbon was added and the mixture was stirred at 25 +/- 5C for 30 min. Water (280 ml) was added, and the mixture was then washed with Toluene (200 ml) and stirred at 25 +/- 5C for half an hour.The aqueous layer was isolated and filtered under reduced pressure with Synter and Hyflo. Thereafter the solution was concentrated under reduced pressure at 40C to half the solution volume. Make-up of the solution was performed to 10 volumes of water versus TBRE. The solution was then heated to 40-45 C. CaCl2 2N (4.1 g + 20 ml water ) was EPO <DP n="17"/>added dropwise to the aqueous phase over 1 hour at 38-45C, forming a suspension. The suspension was then cooled to 25 +/- 50C, stirred at 25 +/- 5C for lhr, filtered and washed with water (3x20 ml) to get a powdery compound (18.1 g dry, 95 %, Chloride content 0.1 % by weight).; Example 5: Level of pH before extraction-12.6; A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (200 niL), water (120 ml), and t-Butyl-Rosuvastatin (40 g), forming a suspension. To this suspension, NaOH 47 % 1.2eq (7.6 g) was added dropwise at 25 +/- 5C. Water (280 ml) was added, forming a mixture. The mixture was then washed with Toluene (200 ml) and stirred at 25 +/- 5C for half an hour.The aqueous layer was i...
	With sodium tetrahydroborate; ethanol; water; at 25℃; for 2h;Product distribution / selectivity;	Example 10: addition OfNaBH4; A 1000 ml reactor equipped with a mechanical stirrer was charged with EtOH (100 mL), water (60 ml), t-Butyl-Rosuvastatin (20 g), and NaBH4 (0.1 g). To the resulting suspension, NaOH 47 % l.leq (3.5 g) was added dropwise at 25 +/- 5C to form a mixture. The mixture was stirred at 25 +/- 5C for two hours and then filtered under reduced pressure with a Sinter. Water (140 ml) was added and the mixture was acidified with HCl 0. IM until PH 8-10. The mixture was then washed with Toluene (100 ml) and stirred at 25 +/- 5C for half an hour.The aqueous layer was isolated. To the aqueous phase active carbon was added and the solution was stirred at 25 +/- 5C for 30 min. The solution was filtered under reduced pressure with Sinter and Hyfio to eliminate the active carbon present. Thereafter the solution was concentrated under reduced pressure at 40C to half the solution volume. Make-up of the solution was performed to 10 volumes of water versus TBRE. The solution was heated to 40-45 0C. CaCl2 (4.13 g) was added dropwise to this solution over 30-90 min at 38-450C, forming a suspension. The suspension was then cooled to 25 +/- 5C, stirred at 25 +/- 5C for lhr, filtered and washed with water (4x20 ml) to get a powdery compound (17.3 g dry, 92 %, Chloride content 0.02 % by weight).
56 g	With water; sodium hydroxide; In ethanol; at 25 - 30℃; for 3h;	To a stirred solution of tertiary butyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-( -methyl-N- methylsulfonylamino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenoate (152 grams, obtained in the above step) in ethanol (208 mL) and water (125 mL) was added 45 % aqueous sodium hydroxide solution (20.5 grams). After stirring for 3 hours at 25 C to 30 C, solvent was completely removed under vacuum and diluted with water (250 mL). The aqueous layer was washed with methyl tert-butyl ether (3 x 250 mL) and the aqueous layer was completely removed under vacuum to obtain the crude product. The resulting crude material was added methyl tert-butyl ether (1500 mL) and cooled to 0 C. The resulting mixture was stirred for 15 hours at 0 C, filtered and washed with methyl tert- butyl ether (2 x 100 mL), dried at 45 C to 50 C to obtain the title compound (56 grams). Yield: 78 %. - NMR (CDC13 , delta ppm): 1.19 (d, 6H), 1.27 (m, 1H), 1.47 (m, 1H), 1.83 - 1.88 (m, 1H), 2.02 - 2.06 (m, 1H), 3.43 (s, 3H), 3.53 (s, 3H), 3.6 (m, 1H), 4.18 (m, 1H), 5.14 (b, 1H), 5.49 - 5.53 (dd, 1H), 6.46 - 6.5 (dd, 1H), 6.8 (b, 1H), 7.24 - 7.28 (m, 2H), 7.7 (m, 2H); Mass (m/z): 482.5 [M+H] +

Reference： [1]Patent: WO2006/136408,2006,A2 .Location in patent: Page/Page column 12-14; 16; 17
[2]Patent: US2017/22169,2017,A1 .Location in patent: Paragraph 0048
[3]Patent: WO2004/103977,2004,A2 .Location in patent: Page 27
[4]Patent: WO2009/47576,2009,A1 .Location in patent: Page/Page column 23-24
[5]Patent: KR2016/120532,2016,A .Location in patent: Paragraph 0199-0200
[6]Patent: WO2005/23778,2005,A2 .Location in patent: Page/Page column 13-18
[7]Patent: WO2006/136408,2006,A2 .Location in patent: Page/Page column 14-15
[8]Patent: WO2007/22366,2007,A2 .Location in patent: Page/Page column 14-20
[9]Patent: WO2007/22366,2007,A2 .Location in patent: Page/Page column 18
[10]Patent: WO2015/8294,2015,A1 .Location in patent: Page/Page column 26-27

4
[ 289042-12-2 ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride; In tetrahydrofuran; water; at 10℃; for 4h;	Add the above product to a three-necked flask6-[ (1E)-2-(4-fluorophenyl)-6-isopropyl-2-(methyl(methylsulfonyl)amino]-5-pyrimidin]-vinyl]-2,2-di Methyl-1,3-dioxane-4-acetic acid tert-butyl ester32.3 grams,Add 330 ml of THF and 33 ml of dilute hydrochloric acid (0.6 mol/L).The reaction was carried out at a temperature of 9 C for 3.5 hours.After the reaction is completed, the solvent is evaporated to dryness.Purification by column yielded 28.58 g of product.The yield was 95% and the purity was 99%.
86%	With water; trifluoroacetic acid; at 30 - 40℃;	To a solution of acetonide protected tert-butyl ester of rosuvastatin (II) (25 g) a dilute solution of TFA in water (2.5 g in 25 mL water) was added at 30-40 C. The reaction was stirred for 30 minutes to 1 hour and then water (25 mL) was added to it. The reaction mixture was again stirred for 3-4 hours at the same temperature. Then an aqueous solution of sodium hydroxide (3.46 g in 100 mL water) was added and the reaction mixture was stirred for 1 hour. The reaction mixture was further diluted with water (200 mL) and washed with toluene (2 x 250 mL) and MTBE (125 mL). MTBE (250 mL) was further added to the aqueous layer. Then sodium chloride (6.25 g) was added to the reaction mixture. An aqueous solution of sodium bisulphate (15 g in 100 mL of water) was added to the reaction mass and the pH was adjusted to 2.4. The organic layer was separated. The aqueous layer was again extracted with MTBE (200 mL) and the combined organic layer was washed with sodium chloride solution (125 mL). A solution of tert-butyl amine (7.91 g) in MTBE (250 mL) was added to the reaction mixture and stirred for 2-6 hours. The reaction mixture was cooled to 15-20 C and stirred at this temperature for 1 hour. The precipitated solid was isolated and dried. The solid was suspended in a mixture of acetonitrile (62.5 mL) and IPA (62.5 mL) and heated to a temperature of 50-55 C for 1-3 hours. The reaction mixture was then cooled to 25-35 C and stirred at this temperature for 2-6 hours. The reaction mixture was further cooled to 10-15 C and stirred for 1 hour. The precipitated solid was filtered, washed with a mixture of acetonitrile and IPA and dried to provide the title compound.Yield: 20.5 g (86 %)Purity by HPLC: 99.82 %
57%	With camphor-10-sulfonic acid; In water; acetonitrile; at 20℃; for 0.5h;	A solution of the compound of formula (39) (7.0 g, 12.1 MMOL) and CAMPHOR-1 0-SULFONIC ACID (2.4 g, 10.4 MMOL) in acetonitrile (50 ml) and water (5 ml) is stirred at room temperature for 30 minutes. It is then diluted with ether and washed successively with saturated sodium hydrogen carbonate solution and brine. The organic phase is dried (using NA2SO4). The salt mixture is filtered off and the filtrate obtained is concentrated by evaporation. The concentrated crude product is dissolved in ethyl acetate and made to crystallise by adding hexane. In that manner, 1.6 G (57 %) of the desired product (41) can be obtained in the form of colourless crystals. 'H NMR (300 MHz, DMSO-DE) : 1.22 (d, J = 6.7 Hz, 6H); 1.32-1. 44 (m, 1H) ; 1. 38 (s, 9H); 1.49-1. 59 (m, 1H); 2.20 (dd, J = 15.0, 7.9 Hz, 1H); 2.28 (DD, J = 15.0, 5.3 Hz, 1H); 3.39-3. 47 (m, 1H) ; 3.44 (s, 3H); 3.53 (s, 3H); 3.74-3. 85 (M, 1H) ; 4.14-4. 22 (m, 1H) ; 4.64 (d, J = 5.3 Hz, 1H) ; 4.89 (d, J = 4.7 Hz, 1H) ; 5.51 (dd, J = 16.1, 5.6 Hz, 1H) ; 6.51 (dd, J = 16. 1,1. 2 Hz, 1H) ; 7.25 (dd, J = 8.8, 8.8 Hz, 2H); 7.70 (dd, J = 9.1, 5.6 Hz, 2H). 13C NMR (75 MHz, DMSO-DB) : 22.4, 28.6, 32.1, 34.0, 42.4, 44.4, 44.9, 65.9, 69.2, 80. 2, 115.7 (JCF = 21.7 Hz), 122.1, 122.4, 132.8 (JCF = 8.7 Hz), 135.1 (JCF = 3.2 Hz), 141.9, 157.4, 163.2 (JCF = 249 Hz), 163.4, 171.1, 174.9. HPLC: CHIRALCEL OD (0.46x25 cm), hexane: EtOH 95: 5,1 ml/min, TR = 19.2 min, S 98 % ee.

		Example-1:50.0 g of alkyl ester diol protected derivative of rosuvastatin of formula (II) was taken in 750 mL of methanol under stirring to prepare a solution. A solution was maintained at temperature of about 55 to 65C, then the mixture of oxalic acid (12g) and water (250ml) is added slowly within lhr time. After complete addition, solution was gradually cooled first at 25C-35C and then further at 10C-20C. 17 mL of Liq. ammonia was added to adjust the pH between 8-9 and solution was for 1 hr. The product was filtered and washed with 2*50mL MeOH-.tfcO (1:1). The above wet cake was taken in 500 mL water and heated to 40C-45C and stirred for 1 hr. further filter wash with hot water (Water temperature is 40-450C). Dry the cake to get 42 g of Rosuvastatin diol ester.
27 g	With hydrogenchloride; water; In acetonitrile; at 25 - 55℃;pH 2.5;	EXAMPLE-7PREPARATION OF (3R,5S,6E) 7-[4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[N.- METWYL(N-METHYLSULFONYL)AMINOIPYRIMIDIN-5-YLI-3,5-DIJ{YDROXY-6-HEPTENOIC ACID, tert-BUTYL ESTER [ROSUVASTATIN tertBUTYL ESTER]Diprotected tert-butyl Rosuvastatin (30 g, 0.052 mole) was suspended in acetonitrile (210 ml) and water (70 ml) at 25-30C. The pH of the reaction mass was adjusted to 2.5 with dilute hydrochloric acid (0.1 molar). Thereafter, the reaction mass was heated to 50-55C and progress of the reaction was monitored by HPLC. After completion of reaction, pH of the reaction mass was adjusted to 8.5 with aqueous ammonia and stirred for 30 mm. Product was filtered and dried at 40-45C under reduced pressure to obtain title compound.Yield: 27gChromatograpbic Purity (by HPLC): 99.7%, Lactone diastereomer: 0.03%
	With hydrogenchloride; In water; acetonitrile; at 35 - 40℃;	To a solution of compound IV (wherein X=0 and R2=tert-butyl; 100 gms) in acetonitrile (700 mL) at 35C to 40C was added 0.05M aqueous HCl solution (300 mL). Stirred the reaction mass at 35C to 40C until reaction completion and cooled to 0C to 5C. Added 1.0 M aqueous sodium hydroxide solution (300 mL), temperature was raised to 25 C to 35C and stirred until reaction completion. Cooled the reaction mass to 0C to 5C, pH was adjusted to 3.4 to 4.0 with 1M aqueous HCl solution (300 mL) and extracted with ethyl acetate. Washed the organic layer with 10% aqueous sodium chloride solution and concentrated under vacuum. Charged ethyl acetate (800 mL) to the obtained residue followed by cyclohexane- 1,2-diamine (29.5 gms) over a period of 15-30 min. The reaction mass was stirred at 25C to 35C for 60 mins, cooled to 0C to 5C and stirred for 2 hrs. The precipitated product was filtered and dried to obtain 80 gms of rosuvastatin cyclohexane- 1,2-diamine salt as white solid. HPLC Purity: >99% The XRPD is set forth in Figure 1.
	With hydrogenchloride; In water; acetonitrile; at 35℃; for 5h;	(2) Preparation of sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl) amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV) To a 5 L four-necked flask, 2 L (10 mL/g) of acetonitrile and 200 g (1 mol) of tert-butyl 6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methanesulfonyl)amino]-5-pyrimidinyl]vinyl]-2,2-dimethyl-1,3-dioxane-4-acetate (compound III) were added, and stirred to homogeneity, followed by adding 14.8 g (0.02 mol, calculated from titrated content) of an aqueous solution of hydrochloric acid having a mass percentage concentration of 0.06%. The system was warmed up to 35 C. and stirred at the same temperature for 5 hours until compound III was completely consumed. To the reaction system was added dropwise 32.5 g (1.1 mol) of an aqueous solution of sodium hydroxide having a mass percentage concentration of 4%, and stirred at 20 C. for 7 hours until the dihydroxy ester intermediate produced in the first phase was completely consumed. The system was concentrated to remove acetonitrile, followed by adding 2 L (10 mL/g) of purified water, and stirred to clearness. The system was extracted three times with 400 mL (2 mL/g) of methyl tert-butyl ether. The aqueous phase was further concentrated until no organic solvent was left, to give the an aqueous solution of the product, sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV), with a purity of >98% and a yield of 97%.
	With hydrogenchloride; In water; acetonitrile; at 35 - 40℃; for 3h;	The method for synthesizing the rosuvastatin calcium chiral isomer impurity of the present embodiment comprises the following steps:(1) 20g compound I was added to 500mL three reaction flask, stirred and dissolved in 220mL of acetonitrile was added dropwise 60mL 0.05M hydrochloric acid, the reaction was incubated dropwise at 35 ~ 40 C for 3 hours until the starting material disappeared (TLC: Ester: petroleum ether = 6: 1),The pH was adjusted to neutral with 5% sodium bicarbonate solution, the acetonitrile was removed by distillation under reduced pressure, extracted twice with methylene chloride (100 mL * 2), dried over anhydrous sodium sulfate, filtered,The filtrate was transferred to 500mL three reaction flask, 60g of manganese dioxide was added, the reaction was refluxed for 20 hours, the reaction was over, filtered, the filtrate was evaporated under reduced pressure and concentrated to dryness to give 17.6g light yellow oil, namely compound III, directly into the next reaction; The yield of compound III was 95.2%
	With hydrogenchloride; In water; acetonitrile; at 25 - 30℃;	Charged tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate (100.00 gm.) in acetonitrile ( 1000.00 ml) at 25-30C and stirred the reacti on mass for 10 mi n. at25-30C. Slowly charged previously prepared hydrochloric acid solution in 45-60 min (0.02M, 200.0 M L) at 25-30C. At this temperature, the reaction mass will get clear. Cooled reaction mass to 22-27C, stirred and maintained the reaction mass until the completion of the reaction, tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate NMT: 1.00 % by H PLC), slowly added sodium hydroxide solution (1.125M, 200.0ml) to reaction mass at 20-25C; maintained the reaction mass at 20-25C. until the completion of reaction, (3R,5S,E)-tert-butyl 7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate estercontent NMT: 1.00 % by H PLC), chilled the reaction mass to -5 to -8C, slowly added the hydrochloric acid solution to adjust the pH 3.5 - 4.0 at the same temperature. Stirred the reaction mass for 15 min at -5 to -8C; charged Sodium Chloride 50.00 gm at -5 to -8C; stirred the reaction mass for 15 mi n at -5 to -8C . T he reacti on mass was al I owed to settl e for 15-20 mi n at - 5 to 0C. Layers were separated and charged organic layer in a separate flask; slowly added Tert. Butyl amine (20.00 gm) at 5 to 15C. After the addition, the temperature of the reaction mass was raised to 20-25C; stirred & maintained reaction mass for 60 min at 20-25C. The temperature of the reaction mass was raised to 30-35C and distilled out acetonitrile completely under vacuum below 45C; degassed the reaction mass under vacuum below 45C. Charged mixture of acetonitrile 450.00 ml, Ethyl acetate 40.0 ml and Methanol 10.0 ml to the degassed reaction mass below 45C; raised the temperature of reaction mass to 55-60C; stirred the reaction mass for 30 min at 55-60C; cooled the reaction mass at 25- 30C; stirred the reaction mass for 60 min at 25-30C; filtered the solid & washed with acetonitrile 100.0 ml at 25-30C to obtain wet material of Rosuvastatin Tert- Butyl Amine Salt i.e., (2-methylpropan-2-amine(3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamide)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate). Yield: 65-70 gm. (78% ) H PL C purity: 99.65% .
	With hydrogenchloride; In water; acetonitrile; at 30 - 40℃;Inert atmosphere;	Under nitrogen protection, 135.0 g of compound 1 and acetonitrile 500.g were placed in a dry and clean reaction flask; Control internal temperature 30.0 ~ 40.0 C, add 0.02M hydrochloric acid 300g, add dropwise, heat preservation 3.0 ~ 4.0 hours; medium control (HPLC: compound 1 ? 1.0%); After the reaction is finished, the temperature is lowered; the internal temperature is controlled at 20.0 to 25.0 C, and 300 g of 1 M sodium hydroxide is added dropwise, and the mixture is kept for 1.0 to 1.5 hours after the incubation (HPLC: compound 2 ? 1.0%); After the reaction is completed, the temperature is lowered; the internal temperature is controlled to be 0.0 to 5.0 C, 130.0 g of sodium chloride is added, and 1 M hydrochloric acid is added dropwise to adjust the pH to 4.0 to 5; after the dropwise addition, the layer is allowed to stand, and the organic phase is dried by adding 135 g of anhydrous sodium sulfate. Filtration, the filter cake is washed with acetonitrile; the combined organic phase is cooled to 0.0-5.0 C, 40 g of 36% aqueous solution of methylamine is added dropwise; the dropwise addition is finished, the internal temperature is controlled to 0.0-5.0 C, and the temperature is maintained for 1.0 hour; After the heat preservation, filtration, the filter cake was rinsed with acetonitrile; crude methylamine saltThe wet product is placed in a vacuum oven; the water bath temperature is controlled at 30 to 35 C, the vacuum degree is ? -0.09, and the vacuum is dried for 8 to 12 hours; After the end of the drying, a crude methylamine salt (115.7 g, yield: 96%; HPLC: 99.30%; diastereomer, 0.70%) was obtained.

Reference： [1]Patent: CN103936680,2016,B .Location in patent: Paragraph 0030; 0032; 0038; 0040; 0046; 0048; 0054; 0056
[2]Patent: WO2012/172564,2012,A1 .Location in patent: Page/Page column 22-23
[3]Patent: WO2004/103977,2004,A2 .Location in patent: Page 26-27
[4]Patent: WO2007/99561,2007,A1 .Location in patent: Page/Page column 8; 9
[5]Patent: WO2014/108795,2014,A2 .Location in patent: Page/Page column 18
[6]Patent: WO2016/125086,2016,A1 .Location in patent: Page/Page column 30
[7]Patent: US2017/22169,2017,A1 .Location in patent: Paragraph 0048
[8]Patent: CN107382875,2017,A .Location in patent: Paragraph 0034-0036; 0042
[9]Patent: WO2019/8593,2019,A1 .Location in patent: Page/Page column 7; 8
[10]Patent: CN109651259,2019,A .Location in patent: Paragraph 0053-0055

5
[ 355806-00-7 ]
[ 287714-41-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; ethanol; water; at 20℃; for 2h;Product distribution / selectivity;	A l L reactor equipped with a mechanical stirrer was charged with EtOH (3 L), water (1800 mL), and TBRE (600 g), forming a reaction mixture. NaOH (47%, 1.2 eq, 114 g) was slowly added to the reaction mixture, at RT. The reaction mixture was stirred at about RT for two hours. The reaction mixture was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present. The reaction mixture was concentrated under reduced pressure at about 40C until half the volume of the reaction mixture remained. Water (2000 mL) was added to the reaction mixture and the reaction mixture was stirred at about RT for 5 minutes. An aqueous phase and an organic phase formed. The phases were separated, and the aqueous phase was washed with ethyl acetate (3000 mL) and stirred at RT for half an hour. The organic phase was discarded. The aqueous phase was concentrated under reduced pressure at about 400C until half the volume remained. Water (2800 mL) was added to the aqueous phase and the aqueous phase was stirred at about RT for 5 minutes. CaCl2 (124 g) was added to the aqueous phase in portions over a period of about 10 minutes at a temperature of about RT. The aqueous phase was then stirred at about RT for about 1 hour, filtered, and washed with 1200 mL of water, yielding a powdery compound (491 g, 88%).Example 18: Conversion of compound 22TB into rosuvastatin Ca with extraction in toluene A 500 mL reactor equipped with a mechanical stirrer was charged with EtOH(150 mL), water (90 mL), and 22TB (30 g), forming a reaction mixture. NaOH (47%, 1.2 eq , 5.7 g) was slowly added to the reaction mixture at a temperature of about RT. EPO <DP n="30"/>The reaction mixture was stirred at RT for about 2 hours. The reaction mixture was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present. The reaction mixture was washed with toluene (150 mL) and stirred at RT for about half an hour, forming an aqueous phase and an organic phase. The two phases were separated, and the organic phase was discarded.The aqueous phase was concentrated under reduced pressure at about 400C until half the volume remained. Water (104 mL) was added to the aqueous phase and the aqueous phase was stirred at about RT for 5 minutes. CaCl2 (6.2 g) was added dropwise to the aqueous phase over 1 minute at about RT. The aqueous phase was then stirred at RT for about 1 hour, filtered, and washed with 1200 mL of water, yielding a powdery compound (26 g, 92%).Example 19: Conversion of compound 22TB (TBRE) into rosuvastatin Ca with extraction in toluene A l L reactor equipped with a mechanical stirrer was charged with EtOH (300 mL), water (90 ml), and 22TB (60 g), forming a reaction mixture. NaOH (47% 1.2eq, 11.4 g) was added dropwise to the reaction mixture at RT. The reaction mixture was stirred at about RT for two hours. The reaction mixture was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present. Water (420 ml) was added to the reaction mixture.The mixture was then extracted with toluene (3000 mL) and stirred at RT for half an hour. An aqueous phase formed and was isolated. The aqueous phase was concentrated under reduced pressure at 400C to half of the volume. Half of the remaining aqueous phase was transferred to a 500 mL reactor and water (110 mL) was added, creating a solution. The solution was stirred at RT for 5 minutes.Ca(OAc)2 (8.8 g) was added dropwise to the solution over 1 min. at RT. The solution was stirred at RT for 1 hour, filtered, and washed with 60 mL of water, yielding a powdery compound (26 g, 94%).
		Example 7; General procedure for preparing isolated ammonium salts of rosuvastatin; 5 g of terf-butyl ester of rosuvastatin 1.75 ml of 8 M NaOH 25 ml of demineralized water 10 ml of tetrahydrofuran EPO <DP n="19"/>The reactants and the solvents are stirred from 50 to 55C for 1 hour. The solution formed is then allowed to cool to room temperature and washed with 50 ml methylcyclohexane yielding 33 ml of aqueous solution of sodium salt of rosuvastatin.To 33 ml of sodium rosuvastatinate solution prepared in the above described experiment is added 1.3 ml 85% phosphoric acid, previously dissolved in 5 ml of water. Reaction mixture is extracted with 40 ml of /so-butyl acetate. Organic layer is separated off and dried with 5 g of anhydrous magnesium sulphate. Drying agent is filtered off and washed with 10 ml /so-butyl acetate obtaining 52 ml of filtrate containing rosuvastatinic acid, which is divided into smaller portions for preparing various ammonium salts.To 5 ml of the obtained solution 1.5 equivalents of appropriate amine and 5 ml tert-butyl methyl ether are added. Rosuvastatin substituted ammonium salt is filtered off and dried on filter. The following solid salts are prepared:cyclohexylammonium salt of rosuvastatin: 0.45 g, 99.71% area by HPLC;1H-NMR: (CD3OD): 1.10 - 1.45 (12H,m), 1.31 (6H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.72 (1 H,m), 1.80 - 1.87 (2H,m), 1.97 - 2.03 (2H,m), 2.25 (1H,dd, J1=MHz, J2=7.6Hz), 2.34 (1H,dd, J1=MHz1 J2=4.9Hz), 2.98 - 3.09 (1 H,m), 3.51 (1H,h, J=7Hz), 3.52 (3H,s), 3.54 (3H,s), 3.92 - 3.97 (1H,m), 4.33 - 4.40 (1H,m), 5.56 (1 H,dd, J1=^Hz, J2=6Hz), 6.62 (1H,dd, J1=^Hz, J2=1.2Hz), 7.14 - 7.22 (2H,m), 7.69 - 7.75 (1H,m);dicyclohexylammonim salt of rosuvastatin: 0.35 g, 99.82% area;1H-NMR: (CD3OD): 1.12 - 1.76 (20H,m), 1.29 (d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.72 (1H,m), 1.83 - 1.92 (4H,m), 2.01 - 2.09(4H,m), 2.25 (1H,dd, J1=HHz, J2=7,6Hz), 2.34 (1H,dd, J1=MHz, J2=4.9Hz), 3.07 - 3.17 (2H,m), 3.51 (1H,h, J=7Hz), 3.52 (3H,s), 3.54 (3H,s), 3.92 - 3.97 (1H,m), 4.33 - 4.40 (1H,m), 5.56 (1H,dd, J1=IeHz, J2=6Hz), 6.62 (1H,dd, J,=16Hz, J2=1.2Hz), 7.14 - 7.22 (2H,m), 7.69 - 7,75 (2H,m);pyrrolidinium salt of rosuvastatin: 0.28 g, 99.71% area,1H-NMR: (CD3OD): 1.29 (6H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.72 (1H,m), 1.96 - 2.01 (4H,m), 2.25 (1H,dd, J1=MHz, J2=7,6Hz), 2.34 (1H,dd, J1=MHz, J2=4,9Hz), 3.20 - 3.25 (4H,m), 3,51 (1H,h, J=7Hz), 3.52 (3H,s), 3.54 (3H,s), 3.92 - 3.97 (1 H,m), 4.33 - 4.40 EPO <DP n="20"/>(1 H,m), 5.56 (1H,dd, J1=IeHz, J2=6Hz), 6.62 (1 H,dd, J1=IeHz, J2=1 ,2Hz), 7.14 - 7.22 (2H,m), 7.69 - 7.75 (2H,m);piperidinium salt of rosuvastatin: 0.28 g, 99.77% area;1H-NMR: (CD3OD): 1.29 (6H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.81 (7H,m), 2.25 (1 H,dd, J1=MHz, J2=7.6Hz), 2,34 (1 H,dd, J1=MHz, J2=4,9Hz), 3.09 - 3.13 (4H,m), 3.51 (1 H,h, J=7Hz), 3.52 (3H,s), 3.54 (3H,s), 3.92 - 3.97 (1H,m), 4.33 - 4.40 (1 H,m), 5.56 (1 H,dd, J1=IeHz, J2=6Hz), 6.62 (1H,dd, J1=^Hz, J2=1.2Hz), 7.14 - 7,22 (1H,m), 7.69 - 7.75 (2H,m);morpholinium salt of rosuvastatin: 0.30 g, 99.51% area;1H-NMR: (CD3OD): 1.29 (6H,d, J=7Hz), 1.49 - 1.57 (1 H,m), 1.62 - 1.72 (1H,m), 2.25 (1 H,dd, J1=MHz, J2=7.6Hz), 2.34 (1 H,dd, J1=HHz, J2=4.9Hz), 3.12 - 3.16 (4H,m), 3.51 (1 H,h, J=7Hz), 3.52 (3H,s), 3.53 (3H,s), 3.81 - 3.,85 (4H,m), 3.92 - 4.00 (1H,m), 4.33 - 4.40 (1H,m), 5.57 (1H,dd, J1=IeHz, J2=6Hz), 6.62 (1H,dd, J1=IeHz, J2=1.2Hz), 7.14 - 7.22 (2H,m), 7.69 - 7.75 (1H,m);1-adamantylammonium salt of rosuvastatin: 0.66 g, 99.75% area;1H-NMR: (CD3OD): 1.29 (6H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.85 (16H,m), 2.15 (3H,s (broad)), 2.25 (1 H,dd, J1=HHz, J2=7,6Hz), 2.34 (1H,dd, J1=UHz, J2=4.9Hz), 3.51 (1 H,h, J=7Hz), 3.52 (3H,s), 3.54 (3H,s), 3.92 - 3.97 (1H,m), 4.33 - 4.40 (1 H,m), 5.56 (1H,dd, J1=IeHz, J2=6Hz), 6.62 (1 H,dd, J1=^Hz, J2=1.2Hz), 7.14 - 7.22 (2H,m), 7.69 - 7.75 (1 H,m).; Example 8; Preparation of N-cyclohexylammonium salt of rosuvastatin; 1O g tert-butyl ester of rosuvastatin3.5 ml 8 M NaOH50 ml demineralized water20 ml tetrahydrofuran EPO <DP n="21"/>The reactants and the solvents are stirred from 50 to 55C for 1 hour. The solution formed is then allowed to cool to room temperature and washed with 100 ml methylcyclohexane yielding 66 ml of aqueous solution of sodium rosuvastatinate.To 33 ml of the obtained solution is added 1.3 ml 85% phosphoric acid in 5 ml demineralized water. Rosuvastatinic acid is extracted with 40 ml /so-propyl acetate. 4.7 g of anhydrous magnesium sulphate and 0.5 g charcoal is added to organic phase and suspension is stirred for 45 min. Magnesium sulphate and charcoal are filtered off yielding 41 ml of filtrate.16 ml of the filtrate is separated and treated by addition of 0.5 ml of cyclohexylamine in 8 ml of /so-propyl acetate during stirring and rosuvastatin cyclohexylammonium salt precipitate instantaneously as white solid. It is separated by filtration, precipitate is washed on the filter with 10 ml of /so-propyl acetate and dried on the filter yielding 1.34 g of the de...
		Example 9; Preparation of crystalline rosuvastatin te/f-octylammonium salt; Rosuvastatin tert-butyl ester (27.0 g, 50.2 mmol) is dissolved in 225 ml of a mixture of tetrahydrofuran and water in the ratio of 4:1 by volume. The clear solution is warmed to 30 0C and 8.0 M NaOH (6.75 ml, 54.0 mmol) is added portionwise. The reaction mixture is stirred at 30 0C for 2 hours giving a clear yellow solution. Then tetrahydrofuran is removed completely under the reduced pressure (20 mbar) at 40 0C. The remaining aqueous solution is diluted with water to 225 ml and washed with ethyl acetate (390 ml). To a vigorously stirring solution of sodium rosuvastatinate is added dropwise HCI 37 % (4.2 ml, 50.2 mmol) at ambient temperature.The obtained white emulsion of rosuvastatin free acid is extracted with ethyl acetate (150 ml). After separation from the organic layer aqueous phase is additionally extracted with ethyl acetate (250 ml). Organic layers are combined and washed with water (3*30 ml). Then ethyl acetate is removed under reduced pressure (20 mbar) at 40 C. The residue is dissolved in a minimal amount of acetonitrile and the solvent is rapidly evaporated under reduced pressure (20 mbar) at 40 0C to give 25.48 g of the solid residue. This solid is then dissolved in acetonitrile (100 ml) to give a clear solution. To a vigorously stirring solution of rosuvastatin free acid is added dropwise tert-octylamine (6.83 g, 50.2 mmol) over 1 minute at EPO <DP n="22"/>ambient temperature. In less then 10 minutes white solid precipitates abundantly from the solution, which cause solidification of the mixture. This solid is then treated with 75 ml of a mixture of hexane and acetonitrile in the ratio of 1:2 mixture by volume to give a dense suspension. The white precipitate is filtered and dried in vacuum at 40 0C to give 27.6 g of a white powder. This powder is suspended in hexane (100 ml) and vigorously stirred for 1 hour at ambient temperature. The undissolved precipitate is collected by filtration, washed with hexane (50 ml) and dried in vacuum at 40 0C to give 27.4 g (89.4 %) of rosuvastatin tert- octylammonium salt as white crystalline powder.Melting point: 121 0C (DSC1 onset)

		B . 7- [4-(4-fluorophenyl)-6-isopropyl-2-(memanesulfonyl-methyl- amino)-pyrimidin-5-yl]- (S^SSydihydroxy-hept-delta-enoic acid zinc salt (2:1)7.54 g (13.96 mmol) of 7-[4-(4-fluorophenyl)-6-isopropyl-2- (methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3i?,55)-dihydroxy- hept-6-enoic acid tert-butylester [compound of the general Formula (III), wherein the meaning of T is hydroxy, R is hydrogen, Q is t-butyl group] obtained in the previous stage are dissolved in 80 ml of ethanol and into this solution 6.98 ml of 2.5 M (17.44 mmol) of sodium hydroxide solution are added dropwise in 20 minutes. Subsequently the reaction mixture is stirred at the temperature of 60 C for 60 minutes. Subsequently the reaction mixture is cooled by using an ice- water mixture to a temperature between 0 and 10 C and at the same temperature, 5.80 ml (17.44 mmol) of 3.0 M hydrochloric acid solution are added thereto dropwise and the stirring is continued for a further 10 minutes. The reaction mixture is evaporated and the residue is extracted with 80 ml of water and 80 ml of ethylacetate.
	With water; sodium hydroxide; at 0 - 35℃;	To a solution of compound IV (wherein X=0 and R2=tert-butyl; 100 gms) in acetonitrile (700 mL) at 35C to 40C was added 0.05M aqueous HCl solution (300 mL). Stirred the reaction mass at 35C to 40C until reaction completion and cooled to 0C to 5C. Added 1.0 M aqueous sodium hydroxide solution (300 mL), temperature was raised to 25 C to 35C and stirred until reaction completion. Cooled the reaction mass to 0C to 5C, pH was adjusted to 3.4 to 4.0 with 1M aqueous HCl solution (300 mL) and extracted with ethyl acetate. Washed the organic layer with 10% aqueous sodium chloride solution and concentrated under vacuum. Charged ethyl acetate (800 mL) to the obtained residue followed by cyclohexane- 1,2-diamine (29.5 gms) over a period of 15-30 min. The reaction mass was stirred at 25C to 35C for 60 mins, cooled to 0C to 5C and stirred for 2 hrs. The precipitated product was filtered and dried to obtain 80 gms of rosuvastatin cyclohexane- 1,2-diamine salt as white solid. HPLC Purity: >99% The XRPD is set forth in Figure 1.
	With sodium hydroxide; In methanol; at 20℃; for 5h;	The reaction flask was charged with a compound of formula VII (26. 8 g, 0.050 mol), methanol 200 ml, 52.5 ml of 1N sodium hydroxide was added at room temperature, and the mixture was allowed to react at room temperature for 5 hours. After completion of the reaction, the solution was neutralized with 1N hydrochloric acid to pH 7.0. Steam to methanol, cooling to 15-20 C, slowly dropping 0.5mol / L of calcium chloride 110ml, filter, wash the filter cake in cold water. Dry to give a white solid. The yield was 87.9%. HPLC purity was 99.7%.
	With hydrogenchloride; In water; at -8 - -5℃; for 0.25h;pH 3.5 - 4;	Charged tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate (100.00 gm.) in acetonitrile ( 1000.00 ml) at 25-30C and stirred the reacti on mass for 10 mi n. at25-30C. Slowly charged previously prepared hydrochloric acid solution in 45-60 min (0.02M, 200.0 M L) at 25-30C. At this temperature, the reaction mass will get clear. Cooled reaction mass to 22-27C, stirred and maintained the reaction mass until the completion of the reaction, tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate NMT: 1.00 % by H PLC), slowly added sodium hydroxide solution (1.125M, 200.0ml) to reaction mass at 20-25C; maintained the reaction mass at 20-25C. until the completion of reaction, (3R,5S,E)-tert-butyl 7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate estercontent NMT: 1.00 % by H PLC), chilled the reaction mass to -5 to -8C, slowly added the hydrochloric acid solution to adjust the pH 3.5 - 4.0 at the same temperature. Stirred the reaction mass for 15 min at -5 to -8C; charged Sodium Chloride 50.00 gm at -5 to -8C; stirred the reaction mass for 15 mi n at -5 to -8C . T he reacti on mass was al I owed to settl e for 15-20 mi n at - 5 to 0C. Layers were separated and charged organic layer in a separate flask; slowly added Tert. Butyl amine (20.00 gm) at 5 to 15C. After the addition, the temperature of the reaction mass was raised to 20-25C; stirred & maintained reaction mass for 60 min at 20-25C. The temperature of the reaction mass was raised to 30-35C and distilled out acetonitrile completely under vacuum below 45C; degassed the reaction mass under vacuum below 45C. Charged mixture of acetonitrile 450.00 ml, Ethyl acetate 40.0 ml and Methanol 10.0 ml to the degassed reaction mass below 45C; raised the temperature of reaction mass to 55-60C; stirred the reaction mass for 30 min at 55-60C; cooled the reaction mass at 25- 30C; stirred the reaction mass for 60 min at 25-30C; filtered the solid & washed with acetonitrile 100.0 ml at 25-30C to obtain wet material of Rosuvastatin Tert- Butyl Amine Salt i.e., (2-methylpropan-2-amine(3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamide)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate). Yield: 65-70 gm. (78% ) H PL C purity: 99.65% .
	With sodium hydroxide; In acetonitrile; at 20 - 25℃;Inert atmosphere;	Under nitrogen protection, 135.0 g of compound 1 and acetonitrile 500.g were placed in a dry and clean reaction flask; Control internal temperature 30.0 ~ 40.0 C, add 0.02M hydrochloric acid 300g, add dropwise, heat preservation 3.0 ~ 4.0 hours; medium control (HPLC: compound 1 ? 1.0%); After the reaction is finished, the temperature is lowered; the internal temperature is controlled at 20.0 to 25.0 C, and 300 g of 1 M sodium hydroxide is added dropwise, and the mixture is kept for 1.0 to 1.5 hours after the incubation (HPLC: compound 2 ? 1.0%); After the reaction is completed, the temperature is lowered; the internal temperature is controlled to be 0.0 to 5.0 C, 130.0 g of sodium chloride is added, and 1 M hydrochloric acid is added dropwise to adjust the pH to 4.0 to 5; after the dropwise addition, the layer is allowed to stand, and the organic phase is dried by adding 135 g of anhydrous sodium sulfate. Filtration, the filter cake is washed with acetonitrile; the combined organic phase is cooled to 0.0-5.0 C, 40 g of 36% aqueous solution of methylamine is added dropwise; the dropwise addition is finished, the internal temperature is controlled to 0.0-5.0 C, and the temperature is maintained for 1.0 hour; After the heat preservation, filtration, the filter cake was rinsed with acetonitrile; crude methylamine saltThe wet product is placed in a vacuum oven; the water bath temperature is controlled at 30 to 35 C, the vacuum degree is ? -0.09, and the vacuum is dried for 8 to 12 hours; After the end of the drying, a crude methylamine salt (115.7 g, yield: 96%; HPLC: 99.30%; diastereomer, 0.70%) was obtained.

Reference： [1]Patent: WO2006/91771,2006,A2 .Location in patent: Page/Page column 28; 28-29; 29
[2]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 17-20
[3]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 20-21
[4]Patent: WO2009/47577,2009,A1 .Location in patent: Page/Page column 37
[5]Patent: WO2016/125086,2016,A1 .Location in patent: Page/Page column 30
[6]Patent: CN103483269,2016,B .Location in patent: Paragraph 0138-0139; 0153-0154
[7]Patent: WO2019/8593,2019,A1 .Location in patent: Page/Page column 7; 8
[8]Patent: CN109651259,2019,A .Location in patent: Paragraph 0053-0055

6
(+)-(3R)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-3-hydroxy-5-oxo-(6E)-heptenoic acid tert-butyl ester [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
90.6%		4.97 g of the compound was placed in a 100 mL round-bottomed flask equipped with a stirrer and a thermometer, and 20 mL of tetrahydrofuran and 5 mL of methanol were added thereto under a nitrogen atmosphere, followed by stirring at room temperature. The reaction temperature was maintained at -78 [deg.] C and 13.3 mL of a 1.0 M solution of triethylborane in tetrahydrofuran was slowly added over 15 minutes. After the addition, the reaction was stirred at this temperature for 0.5 hours and 0.42 g of sodium borohydride was added. The progress of the reaction was confirmed by TLC (Thin Layer Chromatography; Eluent: dichloromethane / ethyl acetate, 2/1). When the reaction was completed, 14 mL of acetic acid was added to the reaction mixture, followed by stirring for 0.5 hour.All. The water layer and the organic layer were separated, and the solvent and low boiling point organic matter were recovered from the organic layer by distillation. Methanol was added to the thus-obtained concentrate, followed by stirring at room temperature for 15 minutes, and concentration was repeated five times. The product was then subjected to silica gel column chromatography (Eluent: dichloromethane / ethyl acetate, 3/1) to give 90.6% yield (Rf = 0.3 (dichloromethane / ethyl acetate, 3/1).
86%		To a solution of 21TB (1 g) in dry THF (26 mL) and dry methanol (7 mL), a solution of diethylmethoxyborane (IM) in THF (2 mL) was added at about -780C, forming a reaction mixture. The reaction mixture was stirred for 0.5 hour, NaBH4 was added, and the stirring was continued for 3 hours. Acetic acid (1.2 mL) was added to the reaction mixture and the reaction mixture was warmed to ambient temperature.Ethyl acetate (150 mL) was added to the reaction mixture and the pH was adjusted to 8 by addition of concentrated NaHCO3 water solution. The layers were separated, and water was extracted by adding an additional amount of ethyl acetate (50 mL). The organic layers were combined and dried over MgSO4. The solvents were then evaporated under reduced pressure, leaving a residue. The residue was treated with methanol and then the methanol was evaporated. Methanol treatment and EPO <DP n="29"/>evaporation was performed two more times, yielding crude compound 22TB (TBRE) (0.87 g, 86%).
	With sodium hydroxide; water; In ethanol; at 20℃; for 2h;	Example 4: Conversion of Compound TBRE into Rosuvastatin Ca with Extraction in TolueneA l L reactor equipped with a mechanical stirrer was charged with EtOH (300 mL), water (90 ml), and 22TB (60 g), forming a reaction mixture. NaOH (47% 1.2eq, 11.4 g) was added dropwise to the reaction mixture at RT. The reaction mixture was stirred at about RT for two hours. The reaction mixture was filtered under reduced pressure with Synter and Hyflo to eliminate the small particles present. Water (420 ml) was added to the reaction mixture.

10.5 g

With sodium tetrahydroborate; diethyl methoxy borane; In tetrahydrofuran; methanol; at -78 - -75℃; for 1.5h;

the reactor internal temperature at -78 , tetrahydrofuran (THF) and 80 mL methanol, 20 mL of the mixture solution to NaBH4(sodium borohydride) 0.9 g (1.3 eq) was added to.After 15 minutes, 50% Et2BOMe in THF solution (diethyl-methoxy-borane, DEMB) was added dropwise 2.33 mL (0.5 eq). formula (R1was dissolved in t-Bu =) 10 g (0.018 mol, 95.2% purity), 20 mL THF to a compound of, was slowly added dropwise thereto for about one hour while maintaining the reactor internal temperature of -78 ~ -75C. After the dropwise addition the internal temperature was stirred for 30 minutes at -78 ~ -75C. After the slow dropwise addition of 10 mL 35% aqueous hydrogen peroxide solution to the reaction solution was heated to an internal temperature of 0 .150 mL of ethyl acetate and 100 mL of purified water was added to the reaction solution and extraction. To remove the water layer and 10% NaHCO3aqueous solution 100 mL, 10% Na2SO3was washed with 100 mL aqueous solution and the organic layer was washed in turn with 10% NaCl solution 100 mL.And concentrated in vacuo at 45 ~ 50C the organic layer formula II (R=t-Bu) as a yellow oil to give the compoundof the to 10.5 g with 94.5% HPLC purity.

Reference： [1]Patent: KR2016/120532,2016,A .Location in patent: Paragraph 0197-0198
[2]Patent: WO2006/91771,2006,A2 .Location in patent: Page/Page column 27-28
[3]Patent: WO2009/9152,2009,A1 .Location in patent: Page/Page column 23
[4]Patent: KR2016/8026,2016,A .Location in patent: Paragraph 0043; 0044

7
[ 910867-13-9 ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 9; Preparation of tert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2- [methyl(methyl sulfonyl)amino]pyrimidin-5-yl}(3R,5S)-3,5-dihydroxyhept-6-enoate tert-Butyl (6E)-7-{4-(4-fiurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl}(5S)-5-hydroxy-3-oxo-6-heptenoate (Ig; 1.87mmol) was taken in 10ml of dry THF/methanol (4:1) and cooled to -780C under nitrogen atmosphere with stirring. To this stirred solution of diethylmethoxyborane (1 M in THF; 2.1g; 2.05mmol)) was added EPO <DP n="17"/>dropwise over a period of ~5 minutes. After stirring for at that temperature for further 30 minutes, NaBH4 (0.08g; 2.05mmol) was added at -78C. The reaction mixture was stirred at -780C for 3-4 hours. To the reaction mixture ImI of acetic acid was added in dropwise followed by 10ml of ethyl acetate and 10ml of water. After stirring for 10 minutes at -78C the reaction mixture was allowed reach 25 -280C. The layers were separated and the aqueous layer was extracted twice with 30ml of ethyl acetate. The combined organic phases were washed twice with 30ml saturated NaHCO3 solution and then with saturated NaCl solution, dried over anhydrous Na2SO4. The reaction mixture was filtered and the solvent was removed by distillation under vacuum. The oily product thus obtained was swapped thrice with 30ml of methanol to remove borate complex and concentrated to obtain an oily mass, which after column purification provided tert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5- yl}(3R,5S)-3,5-dihydroxyhept-6-enoate as a solid.1H NMR (400MHz, CDCl3): 1.23 (6H, d, -CH(CHs)3), 1.4-1.5 (HH, -CH2 -C(CHb)3), 2.34 (2H, d, -CH2COO), 3.31-3.38 (IH, m, -CH(CH3)3), 3.49 (3H, s, -NCH3), 3.54 (3H, s, -SO2CH3), 3.76 (H, bs, -OH), 3.86 (H, bs, -OH), 4.14 (IH, d, >CH-OH), 4.42 (IH, t, >CH-OH), 5.42 (IH, dd, J=15.98 =CHCOO), 6.6 (IH, d, J=I 6.10, -CH=CHCOO), 7.06 (2H, t, Ar-H), 7.63 (2H, dd, Ar-H).
		t-Butyl-(6E)-7-{4-(4-fluorophenyl)-6-isopropyl-2-[N-methyl-iV-methylsulfonyl- amino]pyrimidin-5-yl}-(5S)-5-hydroxy-3-oxo heptenoate (2 g, 0.003 mol) was dissolved in tetrahydrofuran (54 ml) and methanol (14 ml) at 25-3O0C under nitrogen atmosphere. The mixture was cooled to -78C and diethylmethoxy borane (1 ml, 48 % solution in tetrahydrofuran, 0.004 mol) was added to it drop wise at -78C over a period of 10 min. The mixture was stirred at -75C to -78C for one hour and sodium borohydride (0.14 gm, 0.003 mol) was added to it slowly over a period of 15 min. It was stirred for 2 h at -75C to -78C and quenched by adding acetic acid (2 ml) at -78C. Saturated aqueous sodium bicarbonate solution (50 ml) was added to it and stirred for 15 min. The organic layer was separated and aqueous layer was extracted with ethyl acetate (25 ml). The combined organic layer was washed with water (25 ml) and dried over sodium sulfate. The solvent was distilled out at 35- 4O0C under reduced pressure to obtain the title compound. Yield: 2 g1H NMR: 1.27 (d, 6H), 1.47 (s, 9H), 1.50-1.58 (m, IH), 2.38 (d, 2H), 3.37 (septet, IH), 3.51 (s, 3H), 3.57 (s, 3H), 3.63 (bs, IH), 3.80 (bs, IH), 4.15-4.18 (m, IH), 4.44-4.48 (m, IH), 5.46 (dd, IH)5 6.64 (d, IH), 7.09 (t, 2H), 7.65 (dd, 2H).
		EXAMPLE 7; Preparation of t-Butyl-(6E)-7-{4-(4-Fluorophenyl)-6-Isopropyl-2-[N-Methyl-N-Methylsulfonylamino]Pyrimidin-5-yl}-(3R,5S)-3,5-Dihydroxy Heptenoatet-Butyl-(6E)-7-{4-(4-fluorophenyl)-6-isopropyl-2-[N-methyl-N-methylsulfonyl-amino]pyrimidin-5-yl}-(5S)-5-hydroxy-3-oxo heptenoate (2 g, 0.003 mol) was dissolved in tetrahydrofuran (54 ml) and methanol (14 ml) at 25-30 C. under nitrogen atmosphere. The mixture was cooled to -78 C. and diethylmethoxy borane (1 ml, 48% solution in tetrahydrofuran, 0.004 mol) was added to it drop wise at -78 C. over a period of 10 min. The mixture was stirred at -75 C. to -78 C. for one hour and sodium borohydride (0.14 gm, 0.003 mol) was added to it slowly over a period of 15 min. It was stirred for 2 h at -75 C. to -78 C. and quenched by adding acetic acid (2 ml) at -78 C. Saturated aqueous sodium bicarbonate solution (50 ml) was added to it and stirred for 15 min. The organic layer was separated and aqueous layer was extracted with ethyl acetate (25 ml). The combined organic layer was washed with water (25 ml) and dried over sodium sulfate. The solvent was distilled out at 35-40 C. under reduced pressure to obtain the title compound.Yield: 2 g1H NMR: 1.27 (d, 6H), 1.47 (s, 9H), 1.50-1.58 (m, 1H), 2.38 (d, 2H), 3.37 (septet, 1H), 3.51 (s, 3H), 3.57 (s, 3H), 3.63 (bs, 1H), 3.80 (bs, 1H), 4.15-4.18 (m, 1H), 4.44-4.48 (m, 1H), 5.46 (dd, 1H), 6.64 (d, 1H), 7.09 (t, 2H), 7.65 (dd, 2H).

		tert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl}(5S)-5-hydroxy-3-ochio-6-heptenoate (Ig; 1.87mmol) was taken in 10ml of EPO <DP n="21"/>dry THl'Vmcthanol (4:1 v/v) and cooled to -78C under nitrogen atmosphere with stirring. To this stirred solution, dicthylnicthoxyborane ( I M in TMF; 2.1 g; 2.05mmol)") was added drop wise over a period oi' ~5 minutes. After stirring for at that temperature lor further 30 minutes, NaBH1 (0.08g; 2.05mmol) was added at -78C. The reaction mixture was stirred at -78C for 3-4 hours. To the reaction mixture ImI of acetic acid was added in drop wise followed by 10ml of ethyl acetate and 10ml of water. After stirring for 10 minutes at -78C the reaction mixture was allowed reach 25 -280C. The layers were separated and the aqueous layer was extracted twice with 30ml of ethyl acetate. The combined organic phases were washed twice with 30ml saturated NaHCO3 solution and then with saturated NaCl solution, dried over anhydrous Na2SO4. The reaction mixture was filtered and the solvent was removed by distillation under vacuum. The oily product thus obtained was swapped thrice with 30ml of methanol to remove borate complex and concentrated to obtain an oily mass, which after column purification provided lert-butyl (6E)-7-{4-(4-flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5- yl}(3R,5S)-3,5-dihydroxyhept-6-enoate as a solid.1H NMR (400MHz, CDCl3): 1.23 (6H, d, -CH(CHj)3), 1.40-1.50 (HH, m, -C(CjHi)3, -CH2), 2.34 (2H, d, -CH2COO), 3.35 (IH, d, >CH-0H), 3.31-3.38 (IH, m, -CH(CH3)3), 3.49 (3H, s, -NCH3), 3.54 (3H, s, -SO2CH3), 3.76 (H5 s, -OH), 3.86 (H, s, -OH)5 4.41 (IH, d, >CH-0H), 4.42 (IH, t, >CH-0H), 5.42 (IH, dd, J=I 15.98 =CHCOO), 6.6 (IH, d, J= 16.10, -CH=CHCOO), 7.06 (2H, t, Ar-H)5 7.6 (2H, dd, Ar-H).
		Example 13Rosuvastatin t-butyl ester (Compound of Formula IX. where Rg = t-butyl)1 ,0 g t-Butyl 7-(4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidine-5- yl)-5(S)-hydroxy-3-oxo-hept-6(E)-enoate (Compound of Example 12) is dissolved in 6 ml THF and 1 ml methanol under nitrogen. The solution is cooled to -800C and 1 ,0 ml of a 50% solution of methoxydiethylborane in THF is added. The reaction mixture is cooled to -95C and 0,15 g sodium borohydride is added in portions over 2 hours. The reaction mixture is maintained between -90C and 85C for 3,5 hours and 9 hours at room temperature. 0,3 ml of acetic acid is added and the mixture is concentrated by evaporation under reduced pressure. To the residue 3,0 ml of methanol are added and the solvents are distilled off under reduced pressure. The oily residue is dissolved in 10 ml of ethyl acetate and the resulting solution is washed with 3 ml demi water. The organic phase is concentrated by evaporation under reduced pressure at 70C yielding 0,95 g of the product.

Reference： [1]Patent: WO2006/100689,2006,A1 .Location in patent: Page/Page column 15-16
[2]Patent: WO2008/96257,2008,A1 .Location in patent: Page/Page column 21
[3]Patent: US2010/48899,2010,A1 .Location in patent: Page/Page column 12-13
[4]Patent: WO2006/106526,2006,A1 .Location in patent: Page/Page column 19; 20
[5]Patent: WO2007/17117,2007,A1 .Location in patent: Page/Page column 30

8
[ 355806-00-7 ]
[ 109-89-7 ]
[ 917805-73-3 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 95 - 100℃; for 3.5h;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14

9
[ 355806-00-7 ]
[ 4747-21-1 ]
[ 917805-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 95 - 100℃; for 2h;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14

10
[ 355806-00-7 ]
[ 75-59-2 ]
[ 917805-79-9 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 40 - 45℃; for 1h;	Example 3; Hydrolysis of terf-butyl ester of rosuvastatin in a solution of strong organic nitrogen bases; The solution of terf-butyl ester of rosuvastatin in a mixture of a base, tetrahydrofuran and water in the ratio of 1:6:15 by volume is stirred at 50C for few hours. The reaction mixture is sampled and analysed by HPLC to find out the completion of reaction. Results are shown in Table 2. EPO <DP n="16"/>

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 14-15

11
[ 355806-00-7 ]
[ 108-18-9 ]
[ 862994-56-7 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 95 - 100℃; for 3h;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14

12
[ 355806-00-7 ]
[ 75-31-0 ]
[ 852820-97-4 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 95 - 100℃; for 2 - 3h;Product distribution / selectivity;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>; Example 4; Preparation of /so-propylammonium salt of rosuvastatin; 7.2 g of terf-butyl ester of rosuvastatin 35 ml of demineralized water 4.5 ml of /so-propylamineThe reactants and water as the solvent are stirred in the autoclave from 98 to 100C for 2 hours. The solution formed is then allowed to cool to room temperature and some very little amount of solid impurities is filtered off. Filtrate is washed twice with 20 ml of /so-propyl acetate and the aqueous phase is then evaporated under reduced pressure at 700C and 15 mbar to remove solvents and /so-propylamine. 7.15 g of white solid residue of rosuvastatin /so-propylammonium salt is collected.This amount is added to 70 ml acetonitrile and the suspension formed is heated under reflux (800C) for 1h. Then, it is left for 2h at O0C. Subsequently, the product is separated by filtration. Yield: 6.7 g of white crystals of the pure product (>99.9% area, HPLC)1H-NMR: (CD3OD): 1.29 (12H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.72 (1H,m), 2.25 (1H,dd, J1=MHz, J2=7,.6Hz), 2.34 (1 H,dd, J1=MHz, J2=4.9Hz), 3.39 (1H,h, J=7Hz), 3.51 (1H,h, J=7Hz), 3.52 (3H,s), 3.53 (3H,s), 3.92 - 4.00 (1H,m), 4.33 - 4.40 (1H,m), 5.57 (1H,dd, J.=16Hz, J2=6Hz), 6.62 (1H.dd, J1=^Hz, J2=1.2Hz), 7.14 - 7.22 (1H,m), 7.69 - 7.75 (1H,m).
	In water; at 98 - 100℃; for 2h;	Alternatively the title compound is prepared as follows:7,2 g t-butyl ester of rosuvastatin (Compound of Example 13) and 4,5 ml J-PrNH2 in 35 ml demi-water are stirred in the autoclave at 98 - 1000C for 2 hours. The solution formed is then cooled to room temperature and some very little amount of solid impurities is filtered off. Filtrate is washed 2 x 20 ml i-PrOAc and the water phase is then evaporated under reduced pressure at 70C and 15 mbar to remove solvents and i-propylamine. 7,15 g of white solid residue of rosuvastatin i-propylammonium salt is collected. This amount is added to 70 ml acetonitrile and the suspension formed is heated under reflux (80C) for 1 h. Then, it is being held for 2h at 00C. Subsequently, the product is separated by filtration. Yield: 6,7 g of white crystals of the pure product (>99,9% area, HPLC). 2,0 g of above rosuvastatin i- propylammonium salt, 13 ml demi-water and 2,0 ml 1 M calcium acetate are vigorously treated with ultraturax 2 minutes at 10000 rpm under nitrogen and then stirred 10 minutes with magnetic bar at 100C. White precipitate is filtered off and washed with 2 ml demi-water. It is dried 1 hour on the filter and 2 hours at 50 - 600C and at 10 mbars. Yield: 1 ,67 g of rosuvastatin calcium (>99,8%area, HPLC, <0,1% sodium calculated on the content of calcium)

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14; 15
[2]Patent: WO2007/17117,2007,A1 .Location in patent: Page/Page column 31

13
[ 355806-00-7 ]
[ 33966-50-6 ]
[ 917805-75-5 ]

Yield	Reaction Conditions	Operation in experiment
	With water; at 95 - 100℃; for 4h;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14

14
[ 355806-00-7 ]
[ 75-64-9 ]
[ 917805-74-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	In water; acetonitrile; at 25 - 80℃;Product distribution / selectivity;	Example 512.0 g (0.004 mol) of <strong>[355806-00-7]rosuvastatin tert-butyl ester</strong> are suspeded in 14 cm of acetonitrile and 13.4 cm of 1.0 M aqueous TBA solution are added while stirring at 25 C. Thereafter the reaction mixture is heated to 80 C, boiled for 36 hours, evaporated and the remaining water is removed by azeotropic distillation with ethylacetate. The suspension thus obtained is cooled to a temperature between 0 and 5 C, filtered, the filtered solids are washed with cold ethylacetate and dried. Thus 1.90 g (92 %) product are obtained. The product is suspended in 19 cm of acetonitrile, heated to 80 C and 17 cm of isopropanol are added dropwise until dissolution. The thus obtained slightly opalescent solution is filtered and cooled to 25 C in the first step, thereafter to a temperature between 0 and 5 C while stirring. After 2 hours the solids are filtered, washed with cold acetonitrile and dried. Thus 1.70 g (85 %) of product are obtained (HPLC purity: 99.90 %).
	With water; at 95 - 100℃; for 2 - 4h;Product distribution / selectivity;	Example 1; Hydrolysis of terf-butyl ester of rosuvastatin in aqueous solution of amines; 7.5 g of terf-butyl ester of rosuvastatin 38 ml of demineralized water 2 to 5 equivalents of amineThe reactants and water as the solvent are stirred in the autoclave from 98 to 1000C for 1 to 4 hours. The reaction mixture is sampled and analyzed by HPLC ("High Pressure Liquid Chromatography") to find out the completion of reaction. Results are shown in Table 1. EPO <DP n="15"/>; Example 4; Preparation of /so-propylammonium salt of rosuvastatin; 7.2 g of terf-butyl ester of rosuvastatin 35 ml of demineralized water 4.5 ml of /so-propylamineThe reactants and water as the solvent are stirred in the autoclave from 98 to 100C for 2 hours. The solution formed is then allowed to cool to room temperature and some very little amount of solid impurities is filtered off. Filtrate is washed twice with 20 ml of /so-propyl acetate and the aqueous phase is then evaporated under reduced pressure at 700C and 15 mbar to remove solvents and /so-propylamine. 7.15 g of white solid residue of rosuvastatin /so-propylammonium salt is collected.This amount is added to 70 ml acetonitrile and the suspension formed is heated under reflux (800C) for 1h. Then, it is left for 2h at O0C. Subsequently, the product is separated by filtration. Yield: 6.7 g of white crystals of the pure product (>99.9% area, HPLC)1H-NMR: (CD3OD): 1.29 (12H,d, J=7Hz), 1.48 - 1.56 (1H,m), 1.62 - 1.72 (1H,m), 2.25 (1H,dd, J1=MHz, J2=7,.6Hz), 2.34 (1 H,dd, J1=MHz, J2=4.9Hz), 3.39 (1H,h, J=7Hz), 3.51 (1H,h, J=7Hz), 3.52 (3H,s), 3.53 (3H,s), 3.92 - 4.00 (1H,m), 4.33 - 4.40 (1H,m), 5.57 (1H,dd, J.=16Hz, J2=6Hz), 6.62 (1H.dd, J1=^Hz, J2=1.2Hz), 7.14 - 7.22 (1H,m), 7.69 - 7.75 (1H,m). Analogously, tert-butylammonium salt of rosuvastatin is prepared with essentially the same yield:1H-NMR: (CD3OD): 1.29.(6H,d, J=7Hz), 1.35.(9H,s), 1.48 - 1.56.(1 H,m), 1.62 - 1.72.(1H,m), 2.25.(1 H,dd, J,=15Hz, J2=7.6Hz), 2.34.(1H,dd, J1=ISHz, J2=4.9Hz), 3.51.(1H,h, J=7Hz), 3.52.(3H1S), 3.53.(3H,s), 3.92 - 4.00.(1H,m), 4.33 - 4.40.(1 H,m), 5.57.(1 H,dd, J1=^Hz, J2=6Hz), 6.62.(1H,dd, J,=16Hz, J2=I .2Hz), 7.14 - 7.22.(1 H,m), 7.69 - 7.75.(1H,m).
9.3 g		The resulting crude oil phase compound of formula III (R1 = t-Bu) was dissolved in 50 mL of acetonitrile, 50 mL of a 1N NaOH aqueous solution was added dropwise to the reaction solution at 20C. The reaction mixture was stirred at 17 to 22 C for 3 hours. After completion of the reaction, the pH of the mixture was adjusted to 5.2 with 10% aqueous HCl solution and extracted with 100 mL of ethyl acetate. The aqueous layer was removed and the organic layer was washed twice with 70 mL of 10% aqueous NaCl solution. The separated organic layer over anhydrous magnesium sulfate (MgSO4In a) 10 g of dehydrated and filtered, and were concentrated in vacuo at 45 ~ 50 C. Dissolving the thus obtained crude product by rosuvastatin in a yellow oil in 50 mL of methylene chloride and was added followed by tert-butylamine in 3 mL.The reaction mixture was stirred under reflux for 1 hour, the reaction mixture was cooled to room temperature, and then after that 2 sigan cooled and stirred at 0 ~ 5 C filtered and rosuvastatin formula compound of pale yellow and dried for 4 hours at 40 C tert- butyl amine salt was obtained a 9.3 g. 2 step yield 90%, HPLC purity 99.6%, diastereomers (diastereomer) 0.04%, enantiomer (enantiomer)

Reference： [1]Patent: WO2012/73055,2012,A1 .Location in patent: Page/Page column 54-55
[2]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 13-14; 15-16
[3]Patent: KR2016/8026,2016,A .Location in patent: Paragraph 0043; 0045

15
[ 355806-00-7 ]
(E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(methylsulfonyl)amino)pyrimidin-5-yl)-(3R,5S)-3,5-dihydroxyhept-6-enoic acid, calcium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%		The compound of formula IV (17.64 g, 35.6 mmol) prepared in example 5 was reacted withDissolved in ethanol (200 ml), cooled to 0 C, 2N-NaOH aqueous solution (19.6 ml, 39.2 mmol) was added to the reaction solution, The mixture was warmed to room temperature and stirred for 1 hour. The reaction solution was washed with diethyl ether (100 ml x 2)The aqueous layer was cooled to 0 and a solution of CaCl2 (4.35 g, 39.2 mmol) in water (70 ml) was slowly added dropwise. The reaction solution was stirred at room temperature overnight,The white solid was filtered off, washed with water (50 ml x 2) and hexane (50 ml x 2) and dried under reduced pressure. The dried solid was suspended in 20 ml of isopropyl alcohol and stirred for 10 hours, then filtered and washed with isopropyl alcohol and n-hexaneDry under reduced pressure to give a white solidThe rosuvastatin hemicalcium salt (14.8 g)(Yield: 94%).
90%		The compound of formula VII (12.4 g, 0.023 mol), 100 mL of ethanol and 25 mL of 1N lithium hydroxide were added to the reaction flask, and the temperature was raised to 60 C for 8 hours.After completion of the reaction, the ethanol in the reaction mixture was removed, extracted with ethyl acetate, and 46 mL of a 0.5 mol / L aqueous solution of calcium chloride was slowly added dropwise to the aqueous phase. Add and stir for another 30 minutes. The solid was then filtered and the solid was washed with a small amount of water and dried to give 10.0 g of a white solid in 90% yield.
		Example 11; Preparation of rosuvastatin calcium from tert-butyl ester of rosuvastatin via DBU salt; 1.0 g of tert-butyl ester of rosuvastatin0.32 ml of 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU)5 ml of demineralized water2 ml of tetrahydrofuranThe reactants and the solvents are stirred at 500C for 2 h. The solution formed is then allowed to cool to room temperature and 2 ml demineralized water is added. Reaction mixture is washed twice with 10 ml methylcyclohexane. Combined organic phases are washed with 2 ml demineralized water. Combined aqueous phases are partially evaporated reducing original weight for 3.7 g. To remaining solution 0.25 ml of 4M calcium chloride is added during stirring and cooling on ice-bath for 15 minutes. White precipitate of rosuvastatin calcium is filtered off and washed with 1 ml demineralized water. 0.64 g of the desired EPO <DP n="24"/>amorphous product is collected after drying for 12 hours at room temperature in vacuum desiccator.

Example 13; Preparation of rosuvastatin calcium from /so-propylammonium salt of rosuvastatin; 7.5 g of terf-butyl ester of rosuvastatin37 ml of water3.5 ml of /so-propylamine calcium hydroxideThe reactants and the solvent are stirred in the autoclave from 95 to 1000C for 2 hours. Reaction mixture is allowed to cool to room temperature and subsequently 20 ml of demi- water is added. Reaction mixture is washed twice with 37 ml methylcyclohexane. To aqueous phase 0.08 g charcoal is added and the resulting suspension is stirred for 45 minutes. Charcoal and some little amounts of solid impurities are filtered off. Resulting clear solution (containing rosuvastatin /so-propylammonium salt) is evaporated at reduced pressure to oily residue, which is diluted with water to 70 ml of total volume. To the obtained solution of rosuvastatin /so-propylammonium salt is added 2.0 g of moist calcium hydroxide paste (cca 50% content) and resulting suspension is stirred for 1 h at room temperature EPO <DP n="25"/>under nitrogen and for additional 15 min on ice-bath. White precipitate is then filtered off and washed with 8 ml of ice-cold demineralized water. The product is dried under vaccum at 600C for 3 hours. Yield: 6.15 g of amorphous rosuvastatin calcium.

Reference： [1]Patent: KR2016/126700,2016,A .Location in patent: Paragraph 0283-0285
[2]Patent: CN103467458,2016,B .Location in patent: Paragraph 0079; 0081
[3]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 22-23
[4]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 23-24

16
[ 355806-00-7 ]
[ 503610-43-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 16; Preparation of rosuvastatin lactone; 20.0 g <strong>[355806-00-7]rosuvastatin tert-butyl ester</strong>6.5 ml 8M KOH40 ml tetrahydrofuran100 ml demineralized waterThe reactants and the solvents are stirred 1.5 hours from 40 to 45C hydrolysing starting rosuvastatin ester into its potassium salt. The clear solution formed is washed twice with 50 ml methylcyclohexane followed by filtration to remove some little amount of solid impurities. Then, the filtrate is treated with 100 ml ethyl acetate and 4.3 ml of 85% phosphoric acid forming two layers. The upper layer is separated and washed with 20 ml of water. To the organic phase is then added 1.0 ml of 85% phosphoric acid and the reaction mixture is heated 5 minutes on the water-bath of the rotavapor at 500C at atmospheric pressure. Then, the solvent is evaporated at reduced pressure. To the syrupy residue another 100 ml of ethyl acetate is added and the process of heating, evaporation and adding ethyl acetate is repeated three times. At last, the ethyl acetate solution of rosuvastatin lacton is washed with 20 ml of 5% solution of sodium bicarbonate and twice with 30 ml water. The solvent is evaporated at reduced pressure giving 17.0 g of syrupy residue, which crystallized on standing (91% area by HPLC).By consecutive treatment with ultraturrax at 15000 rpm in 80 ml of terf-butyl methyl ether, filtration and recrystallization from /so-propyl acetate / diisopropyl ether the purity is enhanced to 95% area.

Reference： [1]Patent: WO2006/136407,2006,A1 .Location in patent: Page/Page column 24-25

17
[ 355806-00-7 ]
[ 1058749-22-6 ]

Yield	Reaction Conditions	Operation in experiment
		TBRE (10 g) was mixed with IM solution of borane dimethylsulfide complex in THF (56 ml) in an inert atmosphere. The mixture was stirred for 3 h at 2O0C. A solution of NaOH (74 g) in water (5 ml) was slowly added. H2O2 (30% in water, 15 ml) was added dropwise, so that the temperature of the mixture was kept below 5O0C. The mixture was stirred for 0.5 h. A concentrated solution of ammonium chloride (150 ml) was added, and the precipitate was filtered out. The phases were separated and organic phase was first washed with a concentrated solution of sodium sulfite (40 ml), then with a mixture of water (100 ml) and brine (100 ml), and finally with brine (150 ml). Then an organic solvent was removed at reduced pressure, giving a semi-solid residue, containing triol, non-reacted TBRE and some impurities.Triol was isolated by two chromatographic separations. First separation was performed on an RP- 18 column (RediSep C- 18 Reversed Phase Column), using a gradient from 40% to 45% of EtOH in water. The second separation was performed on normal silica column (RediSep Normal Phase Disposable Column), using a gradient from 0% to 1% of EtOH in CH2Cl2 as an eluent. Purity 93%. MS (ES+): M+H-556 M+Na+= 578 RediSep is manufactured by Teledyne Isco, Inc (Nebraska).

Reference： [1]Patent: WO2008/112317,2008,A2 .Location in patent: Page/Page column 20-21

18
[ 355806-00-7 ]
[ 1058749-22-6 ]
rosuvastatin triol calcium [ No CAS ]
crestor [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		2g of material, consisting of TBRE and 2.85% triol-ester (3.7 mmole of the carboxylic group) was suspended in EtOH (10 mL)/water (6 mL) mixture. Saturated NaOH solution (0.35 g, 4.1 mmole) was added dropwise at room temperature and the mixture was stirred for 2 h. The solution was concentrated under vacuum to remove EtOH. Calcium salt was precipitated from the water solution by addition of CaCl2 (0.41g, 3.7 mmole) at 4O0C upon stirring. Stirring was continued for 1 h at room temperature, and the precipitate was filtered, washed with water and dried. The material contained 2.82% Rosu-Ca-triol and 95% Rosu-Ca

Reference： [1]Patent: WO2008/112317,2008,A2 .Location in patent: Page/Page column 21-22

19
[ 1007871-85-3 ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
81 - 84%		Example 10; 7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)- pyrimidin-5-yl]- (3.R,5S)-dihydroxy-hept-6-enoic acid zinc salt (2:1)A. 7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl- amino)-pyrimidin-5-yl]-(3i-s55)-dihydroxy-hept-6-enoic acid tert- butyl-ester10.0 g (17.3 mmol) of (6-{2-[4-(4-fluorophenyl)-6-isoprorhoyl-2- (methanesulfonyl-methyl-amino)-pyrimidin-5 -yl] -vinyl } -2,2-dimethyl- [l,3]dioxan-4-yl)-acetic acid fert-butylester [compound of the general Formula (III), wherein T and R together form an oxymethylene group substituted by two methyl groups, Q is t-butyl group] are dissolved at room temperature in 100 ml of tetrahydrofurane and 50 ml of 10 weight% hydrochloric acid solution are added in 30 minutes. The solution is stirred at room temperature for two hours. Subsequently the reaction is cooled in ice and 2 M sodium hydroxide solution is added until pH 6 (approx. 36 ml) dropwise in a manner that the temperature could not exceed 15 0C. Subsequently 150 ml of water are added and the aqueous solution is extracted twice with 75 ml of dichloromethane each. The organic layer is dried over anhydrous sodium sulfate and evaporated at the pressure of20 Hgmm. The pale yellow oily residue is <n="37"/>crystallized by addition of diisopropylether (20 ml). The white solid is stirred in diisopropylether, filtered and crystallized from the mixture of water (40 ml) and ethanol (35 ml).Yield, 7,54 g (81 %) of 7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3i?,5S)-dihydroxy- hept-6-enoic acid f°rt-butyl-ester.Melting point, 139-140 0C.IR (KBr): 3375, 2976, 1735, 1606, 1542, 1510, 1381, 1340, 1226, 1149, 964 cm"1.1H-NMR (CDCl3, 500 MHz): 7.65 (dd, 2H, J = 8.8, 5.5 Hz), 7.09 (t, 2H, J = 8.7 Hz), 6.64 (dd, IH, J = 16.0, 1.4 Hz), 5.46 (dd, IH, J = 16.1, 5.3 Hz), 4.45 (m, IH), 4.17 (m, IH), 3.84 (m, IH), 3.71 (m, IH), 3.57 (s, 3H), 3.52 (s, 3H), 3.38 (m, IH), 2.38 (d, 2H), 1.52 (m, IH), 1.47 (s, 9H), 1.45 (m, IH)5 1.27 (d, 6H) ppm.13C-NMR (CDCl3, 500 MHz): 174.89, 172.08, 163.42, 163.17 (d, J = 249.5 Hz), 157.23, 139.47, 134.53 (d, J = 3.4 Hz), 132.11 (d, J = 8.3 Hz), 122.50, 121.45, 114.95 (d, J = 21.5 Hz), 81.79, 71.91, 68.58, 42.39, 42.20, 41.87, 33.06, 32.07, 28.06, 21.58, 21.55 ppm.Elemental analysis:Calculated: C 58, 08 H 6,75 N 7,82 S 5,96 %.Measured: C 58, 16 H 6,87 N 7,97 S 5,80 %. Example 117-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)- pyrimidin-5-yl]- (3i?,5S)-dihydroxy-hept-6-enoic acid zinc salt (2:1)A. 7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl- amino)-pyrimidin-5-yl]-(3i?, 55) -dihydroxy-hept-6-enoic acid tert- butylester10.0 g (17.3 mmol) of (6-{2-[4-(4-fluororhohenyl)-6-isoprorhoyl-2- (methanesulfonyl-methyl-amino)-pyriniidin-5-yl]-vinyl}-2,2-dimethyl- [l,3]dioxane-4-yl)-acetic acid fer/-butyl ester [the compound of the general Formula (III), wherein T and R together form an oxymethylene group substituted by two methyl groups, Q is t-butyl group] are dissolved at room temperature in 100 ml of tetrahydrofurane, and 50 ml of 10 volume% hydrochloric acid solution is added in 30 minutes. The solution is stirred for 2 hours at room temperature. The reaction mixture is cooled with ice and 2 M sodium hydroxide solution is added until pH 6 (approx. 36 ml). During the addition of the sodium hydroxide solution, care is taken to keep the temperature of the reaction mixture below 15 0C. Thereafter 150 ml of water is added to the reaction and extracted twice with 75 ml of dichloromethane each time. The organic layer is dried over sodium sulfate and evaporated at the pressure of 20 Hgmm. The pale yellow oily residue is solidified by <n="40"/>mixing with diisopropylether (20 ml). The white solids are stirred with diisopropylether, filtered and recrystallized from the mixture of water (40 ml) and ethanol (35 ml). Yield, 7.81 g (84 %)
81 - 84%		10.0 g (17.3 mmol) of (6-{2-[4-(4-fluororhohenyl)-6-isorhororhoyl-2- (memanesulfonyl-methyl-ammo)-pyrimidm^[l,3]dioxan-4-yl)-acetic acid tert-butylester are dissolved at room temperature in 100 ml of tetrahydrofurane and 50 ml of 10 weight% hydrochloric acid solution are added in 30 minutes. The solution is stirred for further 30 minutes and cooled on ice. With continuous ice cooling, 2 M sodium hydroxide solution are added to the reaction mixture until pH 6 is reached (approx. 36 ml) in such a manner that the temperature of the reaction mixture does not exceed 15 0C. Subsequently 150 ml of water are added and the solution is extracted twice with dichloromethane (75 ml each). The organic layer is dried over sodium sulfate and evaporated at the pressure of 20 Hgmm. After evaporating the solvent, the pale yellow oily residue solidifies upon triturating with diisopropylether (20 ml). The white solids are stirred in diisopropylether, filtered and crystallized from the mixture of water (40 ml) and ethanol (35 ml). Yield, 7.54 g (81 %)Melting point, 139-140 0C. <n="23"/>IR(KBr): 3375,2976, 1735, 1606, 1542, 1510, 1381, 1340, 1226, 1149,964 cm-1.1H-NMR(CDCl3, 500MHz): 7.65 (dd, 2H, J= 8.8, 5.5 Hz), 7.09 (t, 2H, J= 8.7Hz), 6.64 (dd, IH, J= 16.0, 1.4Hz), 5.46 (dd, IH, J= 16.1, 5.3 Hz), 4.45 (m, IH), 4.17 (m, IH), 3.84 (m, IH), 3.71 (m, IH), 3.57 (s, 3H), 3.52 (s, 3H), 3.38 (m, IH), 2.38 (d, 2H), 1.52 (m, IH), 1.47 (s, 9H), 1.45 (m, IH), 1.27 (d, 6H)ppm.13C-NMR (CDCl3, 500 MHz): 174.89, 172.08, 163.42, 163.17 (d, J = 249.5 Hz), 157.23, 139.47, 134.53 (d, J = 3.4 Hz), 132.11 (d, J = 8.3 Hz), 122.50, 121.45, 114.95 (d, J = 21.5 Hz), 81.79, 71.91, 68.58, 42.39, 42.20, 41.87, 33.06, 32.07, 28.06, 21.58, 21.55 ppm.Elemental analysisCalculated: C 58,08 H 6,75 N 7,82 S 5 ,96 %.Measured: C 58,16 H 6,87 N 7,97 S 5 ,80 %.; 10.0 g (17.3 mmol) of (6-{2-[4-(4-fluorophenyl)-6-isopropyl-2- (methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-vinyl}-2,2-dimethyl- [l,3]dioxan-4-yl)-acetic acid tert-butylester are dissolved in 100 ml of tetrahydrofurane at room temperature and 50 ml of 10 weight% hydrochloric acid solution are added in 30 minutes. The reaction mixture is stirred for two hours at room temperature. Subsequently, while cooling on ice, 2 M sodium hydroxide solution is added to the reaction mixture until pH 6 is reached, in a speed that the temperature of the reaction mixture does not exceed 15 0C. Subsequently 150 ml of water are added and the reaction mixture is extracted twice with 75 ml of dichloromethane each. The organic layer is dried over sodium sulfate and evaporated at the pressure of 20 Hgmm. The pale yellow oily residue crystallized upon addition of diisopropylether (20 ml).The white solids are stirred in diisopropylether, filtered and recrystallized from the mixture of water (40 ml) and ethanol (35 ml). Yield, 7.81 g (84 %)

Reference： [1]Patent: WO2009/47577,2009,A1 .Location in patent: Page/Page column 35-36; 38-39
[2]Patent: WO2009/47576,2009,A1 .Location in patent: Page/Page column 21-23

20
[ 1310-73-2 ]
[ 355806-00-7 ]
rosuvastatin sodium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With ethanol; water; at 20 - 60℃; for 4.5h;Product distribution / selectivity;	B . 7- [4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl- amino)-pyrimidin-5-yl]- (3i?,5S)-dihydroxy-hept-6-enoic acid zinc salt (2:1)7.81 g (14.5 mmol) of 7-[4-(4-fluorophenyl)-6-isopropyl-2- (methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3i?,5S)-dihydroxy- hept-6-enoic acid fert-butylester are dissolved in 200 ml of ethanol at room temperature and 58 ml of 0.25 M sodium hydroxide solution (14.5 mmol) are added dropwise in 30 minutes. The reaction mixture is kept at the temperature of 60 C for 4 hours. Subsequently the solution is filtered on a G4 sintered glass filter and the ethanol is evaporated at 20 Hgmm pressure. The residue is mixed with 40 ml of water and extracted three times with 15 ml of ethylacetate each and the aqueous layer is evaporated. From the residue, 10 ml of ethanol is evaporated twice and the remaining solids are stirred in 40 ml of diisopropylether and filtered. Yield, 6.65 g (91 %)The quality of the product is identical in all respects with those of the product obtained in Example 5.

Reference： [1]Patent: WO2009/47577,2009,A1 .Location in patent: Page/Page column 39

21
[ 355806-00-7 ]
[ 122-75-8 ]
[ 1045601-12-4 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 8; Preparation of N,N'-Dibenzylethylenediamine RosuvastatinRosuvastatin t-butyl ester (1 g) was dissolved in ethanol (15 ml). The resulting solution was treated with 1 N aqueous sodium hydroxide (1.96 ml) at 25-30 C. The mixture was stirred for 1 h at 25-30 C. for completion of hydrolysis. Ethanol was rotoevaporated and the residue is diluted with DM water (25 ml) and extracted with a mixture of ethyl acetate - toluene (4:6, 2×20 ml).To the above aqueous layer, a solution of <strong>[122-75-8]N,N'-dibenzylethylenediamine diacetate</strong> (0.34 g dissolved in 2 ml of water) was added and stirred for 2 h. The precipitated product was filtered, washed with water and dried under vacuum at 40-45 C.Dry Wt. 0.75 g

Reference： [1]Patent: US2010/48899,2010,A1 .Location in patent: Page/Page column 13

22
[ 1235588-97-2 ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
95%		h.) Tert-butyl (3.R, 55, E) -7- [4- (4-fluorophenyl) -6-isopropyl-2- (N-methylmethylsulfonamido) -pyrimidin-5-yl] -3, 5-dihydroxyhept- 6-enoate (I)Tert-butyl 2- [ (4.R, 65) -6-{ (E) -2- [4- (4-fluorophenyl) -6-isopropyl- 2- (N-methylmethylsulfon-amido) pyrimidin-5-yl } vinyl) -2-phenyl- 1, 3-dioxan-4-yl] acetate (II) (9.55 g) was dissolved in 80% ace¬ tic acid (50 mL) and stirred 3 h at elevated temperature (40 - 60 0C) . The solvent was evaporated. The oily residue was dis¬ solved in ethyl acetate (40 mL) and washed with 5 % aqueous NaHCO3 and water. The organic phase was dried with anhydrous Na2SO4, filtered and the solvent evaporated to give 7.79 g (95 %) of the title compound as an oily product.
95%	With hydrogenchloride; In tetrahydrofuran; water; at 20℃; for 1h;	The compound of formula III (13.3 g, 21.25 mmol), prepared in step 1,After dissolving in 33 mL of THF at room temperature, 2N HCl (21.2 mL) was added.The solution was stirred at room temperature for 1 hour, then saturated aqueous sodium bicarbonate solution was added until the pH of the reaction solution became 8-9.After the organic layer was washed with saturated sodium hydrogencarbonate (50 mL) and water (50 mL) successively, the organic layer was washed with ethyl acetate (20 mL) and ethyl acetate (20 mL) Was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Ethyl acetate (5 ml) was added to the concentrate, and the solution was dissolved in n-hexane (50 ml), followed by crystallization at room temperature for 3 to 5 hours. The solid was filtered off under reduced pressure, washed with a mixed solvent (10 ml) of cold n-hexane: ethyl acetate = 20: 1 (v / v) and then washed with n-hexane (10 ml) 5.1 g). Ethyl acetate (5 ml) was added to the obtained solid, which was then dissolved by heating at 50 . After cooling to room temperature and addition of n-hexane (10 ml) And slurried for 1 hour. The resulting solid was filtered off under reduced pressure, washed with a mixed solvent (10 ml) of cold n-hexane: ethyl acetate = 20: 1 (v / v), washed with n-hexaneLt; / RTI & gt; The resulting solid was dried under reduced pressure at room temperature to give 10 g (20.18 mmol) of the compound of formula IV (95% yield).

Reference： [1]Patent: WO2010/81861,2010,A1 .Location in patent: Page/Page column 41
[2]Patent: KR2016/126700,2016,A .Location in patent: Paragraph 0205; 0211-0213

23
[ 355806-00-7 ]
[ 122-75-8 ]
(3R,5S,6E)-7-[4-(4-fluorophenyl)-6-(1-methylethyl)]-2-[methyl(methylsulfonyl)amino-5-pyrimidinyl]-3,5-dihydroxy-6-heptenoic acid N,N'-dibenzylethylenediamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 5PREPARATION OF N,N'-DIBENZYLETHYLENEDIAMINEROSUVASTATINRosuvastatin t-butyl ester (1 g) was dissolved in ethanol (15 ml). The resulting solution was treated with 1 N aqueous sodium hydroxide (1.96 ml) at 25-300C. The mixture was stirred for 1 h at 25-300C for completion of hydrolysis. Ethanol was rotoevaporated and the residue is diluted with DM water (25 ml) and extracted with a mixture of ethyl acetate - toluene (4:6, 2 x 20 ml). <n="14"/>To the above aqueous layer, a solution of N.N'-dibenzylethylenediamine diacetate (0.34 g dissolved in 2 ml of water) was added and stirred for 2 h. The precipitated product was filtered, washed with water and dried under vacuum at 40-450C. Dry Wt. 0.75 g

Reference： [1]Patent: WO2008/38132,2008,A1 .Location in patent: Page/Page column 12-13

24
[ 1054627-26-7 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2014/108795,2014,A2
[2]Patent: WO2016/125086,2016,A1

25
[ 141942-89-4 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2014/108795,2014,A2

26
[ 124655-09-0 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2014/108795,2014,A2
[2]Patent: WO2014/108795,2014,A2
[3]Patent: WO2016/125086,2016,A1
[4]Patent: KR2016/126700,2016,A
[5]Patent: KR2016/126700,2016,A
[6]Patent: KR2016/126700,2016,A
[7]Patent: KR2016/126700,2016,A
[8]Patent: KR2016/126700,2016,A
[9]Patent: KR2016/126700,2016,A

27
[ 1353750-24-9 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2014/108795,2014,A2

28
(R)-tert-butyl 4-cyano-3-(tert-butyldimethylsilyloxy)butyrate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

29
(R)-tert-butyl 4-carbamoyl-3-(tert-butyldimethylsilyloxy)butyrate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

30
(R)-5-tert-butoxy-3-(tert-butyldimethylsilyloxy)-5-oxopentanoic acid [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1
[2]Patent: KR2016/120532,2016,A

31
(R)-3-(tert-butyldimethylsilyloxy)-5-ethoxycarbonyloxy-5-oxopentanoic acid tert-butyl ester [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

32
[ 141942-85-0 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

33
tert-butyl (3R)-3-(tert-butyldimethylsilyloxy)-5-oxo-6-triphenylphosphorylidenehexanoate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

34
tertiary butyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R)-3-hydroxy-5-oxo-(E)-6-heptenoate [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate; diethyl methoxy borane; In tetrahydrofuran; methanol; at -80 - 25℃; for 4h;Inert atmosphere;	Tertiary butyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonyl amino) pyrimidin-5-yl]-(3R)-3-hydroxy-5-oxo-(E)-6-heptenoate (188 grams, 0.172 mol, obtained in the above step) was taken in tetrahydrofuran (700 mL) and methanol (174 mL) at 25 C under nitrogen atmosphere. The resulting mixture was cooled to -78 C to -80 C and diethylmethoxyborane (1M) in tetrahydrofuran solution (178 mL) was added to the reaction mixture followed by sodium borohydride (6.8 grams, 0.18 mol) over a period of 1 hour at -78 C to -80 C. After stirring for 3 hours at -78 C to -80 C, acetic acid (20 grams, 0.33 mol) was slowly added in 45 minutes. The reaction mixture was warmed to - 10 C to -15 C and added ethyl acetate (472 mL) and water (472 mL). The temperature of the resulting mixture was raised to 25 C and separated the layers. The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with sodium bicarbonate solution (2 x 270 grams) followed by brine solution (2 x 270 mL). The solvent was distilled off at below 50 C under vacuum to obtain the title compound (153 grams). Yield: 77.2 %, Purity: 46.6 %. - NMR (CDCI3 , 6 ppm): 1.24 -1.34 (d, 6H), 1.46 (s, 9H), 1.53 (m, 2H), 2.36 - 2.38 (d, 2H), 3.35 (m, 1H), 3.51 (s, 3H), 3.5,8 (s, 3H), 3.8 (b, 2H), 4.16 (m, 1H), 4.44 (m, 1H), 5.42 - 5.47 (dd, 1H), 6.6 - 6.64 (d, 1H), 7.0 (t, 2H), 7.62 - 7.65 (dd, 2H); Mass (m/z): 538.4 [M+H] +.

Reference： [1]Patent: WO2015/8294,2015,A1 .Location in patent: Page/Page column 26

35
[ 141942-82-7 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

36
[ 105876-28-6 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2015/8294,2015,A1

37
tert-butyl (6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidin-5-yl]-3,5-dioxohept-6-enoate [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
86.7%	With glucose dehydrogenase; D-Glucose; carbonyl reductase; NADP; sodium carbonate; In ethanol; water; at 30 - 50℃;pH 6.9 - 7.2;Enzymatic reaction;	In 3000 ml in the reaction bottle, by adding 180g compound E, 1000 ml water and 300 ml ethanol, 50g glucose dehydrogenase, 35g carbonyl reductase, 3.5gNADP (coenzyme), 180g glucose. Controlling the reaction temperature 30-33C, dropwise 10% sodium carbonate solution, adjusting PH to 6.9-7.2, reaction 8-10 hours, TLC detection after the reaction, heating to 50 C stirring 1 hour, decompression desolution of the ethanol is removed, cooling, adding 1200 ml ethyl acetate and infusorial earth 100g, is filtered to remove enzyme dregs, heating solution extraction, obtaining organic layer, after de-water washing is dissolved to dry. Adding isopropanol crystallization twice, filtering to obtain 156g compound F, chemical purity 99.3%, optical purity 99.9%, yield 86.7%.

Reference： [1]Patent: CN105367502,2016,A .Location in patent: Paragraph 0009; 0012; 0024

38
[ 108350-21-6 ]
[ 355806-00-7 ]

Reference： [1]Patent: CN105367502,2016,A

39
3-hydroxy-5-oxo-hexanoic acid t-butyl ester [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN105367502,2016,A

40
tert-butyl (6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidin-5-yl]-3-hydroxy-5-oxohept-6-enoate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN105367502,2016,A

41
[ 135054-68-1 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1

42
[ 380460-39-9 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1

43
[ 380460-37-7 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1

44
[ 147118-37-4 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1

45
[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl(methyl)amino)pyrimidin-5-yl-methyl]triphenylphosphonium triflate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1

46
[ 355806-00-7 ]
rosuvastatin, cyclohexane-1,2-diamine salt [ No CAS ]

Reference： [1]Patent: WO2016/125086,2016,A1

47
[ 154026-95-6 ]
[ 355806-00-7 ]

Reference： [1]Patent: WO2016/125086,2016,A1
[2]Patent: KR2016/126700,2016,A
[3]Patent: KR2016/126700,2016,A
[4]Patent: KR2016/126700,2016,A

48
[ 154026-93-4 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

49
tert-butyl 2-((4R,6S)-6-(chloromethyl)-2-phenethyl-[1,3,2]-dioxaboran-4-yl)acetate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

50
tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2-phenethyl-[1,3,2]-dioxaboran-4-yl)acetate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

51
tert-butyl 2-[(4R,6S)-6-formyl-2-phenylethyl-[1,3,2]-dioxaboran-4-yl]acetate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

52
tert-butyl 2-[(4R,6S)-6-[(E)-2-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]ethenyl]-2-(2-phenylethyl)-[1,3,2]-dioxaboran-4-yl]acetate [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
5.6 g	With dihydrogen peroxide; In methanol; acetone; at 15 - 30℃; for 5.5h;	Add 60 mL of methanol and 8.4 mL of acetone to the reactor. (E) -tert- butyl 2- [6- [2- [4- (4-fluorophenyl) -6-isopropyl-2- (N- Yl] vinyl] -2-phenethyl- [1.3.2] -dioxaboran-4-yl] acetate was added and dissolved. After maintaining the temperature of the reaction solution at 25 to 30 C., 13.9 mL of 30% H 2 O 2 was added dropwise at 15 to 20 C. for 30 minutes. When the addition was completed, the reaction was carried out at 25 to 30 C. for 5 hours.After completion of the reaction, 81 ml of acetonitrile is added to the reactor, and the mixture is heated to 33-37 C and stirred for 10 minutes. To the reactor 70 mL of water was added to 15Min for 10 minutes and then add 70 mL of water at 33-37 C for 60 minutes. After the crystals are formed, the mixture is stirred at 33-37 C for 30 minutes. The reaction solution in which the crystals are formed is cooled to 10-20 C, stirred for 60 minutes, and filtered. The filtrate is filtered and vacuumed at an internal temperature of 55-60 C 5.6 g of the title compound were obtained.

Reference： [1]Patent: KR101528359,2015,B1 .Location in patent: Paragraph 0166-0168

53
tert-butyl 2-[(4R,6S)-6-[(E)-2-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]ethenyl]-2-propyl-[1,3,2]-dioxaboran-4-yl]acetate [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
4.2 g	With dihydrogen peroxide; In methanol; acetone; at 15 - 30℃; for 5.5h;	Add 54 mL of methanol and 8 mL of acetone to the reactor. (E) -tert-butyl 2- [6- [2- [4- (4-fluorophenyl) -6-isopropyl-2- (N- methylmethylsulfonamido) 5-yl] vinyl] -2-propyl- [1.3.2] -dioxaboran-4-yl] acetate is added to dissolve. After maintaining the temperature of the reaction solution at 25 to 30 C, 13.0 mL of 30% H 2 O 2 was added dropwise at 15-20 C. for 30 minutes. When the addition was completed, the reaction was carried out at 25-30 C. for 5 hours, After completion of the reaction, 72 ml of acetonitrile is added to the reactor, and the mixture is heated to 33 to 37 C and stirred for 10 minutes. 63 mL of water was added to the reactor for 15 minutesAnd the mixture is stirred for 10 minutes, and then 63 mL of water is added at 33-37 DEG C for 60 minutes. After the crystals are formed, the mixture is stirred at 33-37 C for 30 minutes. The reaction solution in which crystals are formed is cooled to 10-20 C, stirred for 60 minutes, and filtered. The filtrate was taken out and vacuumed to an internal temperature of 55 to 60 DEG C to obtain 4.2 g of the title compound.

Reference： [1]Patent: KR101528359,2015,B1 .Location in patent: Paragraph 0170-0172

54
[ 154026-92-3 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

55
[ 540-88-5 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR101528359,2015,B1

56
[ 1184-85-6 ]
C₂₅H₃₃FN₂O₇S [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
27 g	In acetic acid butyl ester; for 4h;Reflux;	The reaction flask was charged with the crude product of the compound of the formula VII obtained in the previous step 36. 5 g, N-butyl acetate 300 ml, N-methylmethanesulfonamide (7. 4 g, 0. 068 mol), The reaction was refluxed for 4 hours. After completion of the reaction, 300 ml of water was added, Stir for 15 minutes. Layer, anhydrous MgS04 organic layer dry, concentrated under vacuum to half the original volume, drop is added to the burning, precipitation of solid. filter, (Yield: 73.8%, volume 1: purity: 99.3%) as a white solid.

Reference： [1]Patent: CN103483269,2016,B .Location in patent: Paragraph 0136-0137; 0151-0152

57
methyl 4-(4-fluorophenyl)-2-hydroxy-6-isopropylpyrimidine-5-carboxylate [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103483269,2016,B
[2]Patent: CN103467458,2016,B

58
C₁₆H₁₇FN₂O₅S [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103483269,2016,B

59
C₁₅H₁₇FN₂O₄S [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103483269,2016,B

60
C₁₅H₁₆BrFN₂O₃S [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103483269,2016,B

61
C₂₈H₃₇FN₂O₇S [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103483269,2016,B

62
[ 1207460-27-2 ]
[ 124-63-0 ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
12.4 g	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	12.8 g of the compound of the formula VI, 100 mL of dichloromethane,Triethylamine (4.0 mL, 0.029 mol)To a temperature of 0 C, methylsulfonyl chloride (3.1 g, 0.027 mol) was slowly added dropwise.After the dropwise addition, the temperature was raised to room temperature and the reaction was continued for 2 hours.After the TLC test reaction was complete, the pH was adjusted to 3 with 2N aqueous hydrochloric acid and stirring was continued for 3 hours.The reaction mixture was poured into water, 100 mL of ethyl acetate was added,After stratification, the organic phase was washed with saturated aqueous solution of sodium bicarbonate,Saturated salt water washed once, anhydrous MgSO4 dry,Concentrated under reduced pressure to dry,The concentrate was recrystallized from ethyl acetate and n-hexane,To give 12.4 g of a white solid, 92.3% in two steps.

Reference： [1]Patent: CN103467458,2016,B .Location in patent: Paragraph 0077; 0078

63
C₁₄H₁₅FN₂O₂ [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103467458,2016,B

64
C₁₄H₁₃Br₂FN₂ [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103467458,2016,B

65
C₂₇H₃₄BrFN₂O₄ [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: CN103467458,2016,B

66
C₃₈H₆₄FN₃O₆SSi₂ [ No CAS ]
[ 355806-00-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; acetonitrile; at 40℃; for 4h;	(2) Preparation of sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl) amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV) To a 2 L four-necked flask, 1.6 L (8 mL/g) of acetonitrile and 100 g (1 mol) of tert-butyl 6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methanesulfonyl)amino]-5-pyrimidinyl]vinyl]-3,5-bis(tert-butyldimethylsiloxy)-hexanoate (compound III) were added, stirred to homogeneity, followed by adding an aqueous solution of 14.8 g (0.03 mol, calculated from titrated content) of hydrochloric acid having a mass percentage concentration of 0.09%. The system was warmed up to 40 C., and stirred at the same temperature for 4 hours until compound III was completely consumed. To the reaction system was added dropwise an aqueous solution of 11.0 g (1.1 mol) of sodium hydroxide having a mass percentage concentration of 4%, stirred for 2.5 hours, until the dihydroxy ester intermediate produced in the first phase was completely consumed. The system was concentrated to remove acetonitrile, followed by adding 2 L (10 mL/g) of purified water, and stirred to clearness. The system was extracted three times with 300 mL (3 mL/g) of methyl tert-butyl ether. The aqueous phase was further concentrated until no organic solvent was left, to give an aqueous solution of the product, sodium (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoate (compound IV), with a purity of >97% and a yield of 85%.

Reference： [1]Patent: US2017/22169,2017,A1 .Location in patent: Paragraph 0053

67
[ 799842-07-2 ]
[ 355806-00-7 ]

Reference： [1]Patent: US2017/22169,2017,A1
[2]Patent: US2017/22169,2017,A1

68
N-(5-((4,4'-methylphenylphosphoryl)-methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: US2017/22169,2017,A1
[2]Patent: US2017/22169,2017,A1

69
C₂₁H₃₄O₅Si [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

70
[ 615556-98-4 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

71
[ 676256-39-6 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

72
[ 95310-87-5 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

73
[ 128237-30-9 ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

74
C₁₇H₃₄O₅Si [ No CAS ]
[ 355806-00-7 ]

Reference： [1]Patent: KR2016/120532,2016,A

75
tert-butyl 2-((4R,6S)-6-((tert-butyldimethylsilyloxy)methyl)-2-phenyl-1,3-dioxan-4-yl)acetate [ No CAS ]
[ 355806-00-7 ]