Atorvastatin tert-butyl ester

3 g, 4.58 mmol of (4R-cis)-6-{2-[2-(4-fluorophenyl)-5-(1- methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]pyrrole-1-yl]- ethyl}-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tertiary butyl ester (I) is added to a 50 mL reaction flask and suspended in 13.5 mL of acetonitrile, 2.6 mL of water and 0.72 mL of 1M HC1. The reaction mixture is stirred for at least 12h, 30 mL of water was added and the stirring is continued for at least lh. The solid precipitate is filtered off and the filter cake is washed with 1 mL of water. The wet cake is dried at 20-25 °C for 3h and at 45-50 °C for 6h till LOD (Loss on drying) <0.5percent. 185.8 mg, 98.9 percent of [R-(R*, R*)]-2-(4-fluorophenyl)-(3, 8- dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)- carbonyl] -1H-pyrrole-1-heptanoic acid tertiary butyl ester (II) is isolated having a melting range of 100-102 °C. The pu- rity of the obtained product is higher than 99 percent.Put 250 mL of methanol into the reaction flask, 25mL water, 1mL hydrochloric acid, 40g of the compound of formula 5, The mixture was slowly heated to 50 to 55 ° C with stirring, and refluxed for 2 to 3 hours.After the reaction is completed, the temperature is lowered to 15 to 20 ° C, and the pH is adjusted to 5.5 to 6.5 with 1percent sodium hydroxide.The mixture was stirred for 8 to 12 hours, filtered, and the filter cake was washed with 100 mL of methanol. Drying under reduced pressure at 50-60 ° C for 8 hours to constant weight, Recognized as a white powdery solid compound of formula 4, Dry weight 34.5 ~ 36.8g, The yield is 92 to 98percent.The product obtained in the step (a) is dissolved in 4.7 L of methanol and transferred to a 20 L dry clean reaction vessel, and after adding 4.7 L of water, Cool down to 0 ° C -5 ° C, slowly add 6 L of 10 wtpercent dilute hydrochloric acid, control the temperature of the reaction solution does not exceed 25 ° C throughout the dropwise addition process.After the completion of the dropwise addition, the cooling is turned off, the temperature is raised to 25 ° C to 30 ° C, and the mixture is kept warm for 2 hours to 3 hours until the reaction is complete.(TLC detection and tracking, the developing solvent is ethyl acetate: petroleum ether = 1:2) The reaction solution was extracted twice with 2*9 L of toluene, the aqueous phase was discarded, the organic phase was combined, and the mixture was placed in a rotary evaporator and decompressed at 60 ° C. Concentrate to dryness, get(4R-cis)-6-[2-[2-(4-fluorophenyl)-5-(1-isopropyl)-3-phenyl-4-[(aniline)hydroxyl]-1H-pyrrol-1-yl]ethyl]-1, 3-dihydroxy-4-acetic acid tert-butyl ester 1.36 kg, yield 96.7percent, purity 98.8percent.First, 90 mL of methanol and 10 g of Compound L1 were placed in a 250 mL three-necked flask.12 mL of a hydrochloric acid solution having a mass concentration of 5percent was slowly added dropwise, and reacted at 35 ° C for 2 h.TLC monitoring reaction is completed, adding saturated NaHCO3 solution to adjust the pH value of the reaction system is 7;Filtering, washing the filter cake with 25 mL × 2 distilled water, and drying at 60 ° C;The obtained crude atorvastatin tert-butyl ester and 30 mL of isopropanol were added to a 50 mL single-mouth bottle for 30 min, frozen and decrystallized, suction filtered, washed with 5 mL of frozen isopropanol, and blast dried at 60 ° C.The weigh was 9.53 g, the yield was 95.3percent, and the purity was 99.97percent.10 g, 15.3 mmol of (4R-cis)-6-{2-[2-(4-fluorophenyl)-5-(1- methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]pyrrole-1-yl]- ethyl}-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tertiary butyl ester (I) is added to a 500 mL reaction flask and suspended in 45 mL of acetonitrile, 18.8 mL of water and 2.4 mL of 1M HC1. The reaction mixture is heated to 45 °C until all starting ma- terial is dissolved and the reaction is followed by HPLC method. After 4 h the reaction mixture is cooled to room tem- perature, and 100 mL of water is added. The solid precipitate is filtered off and the cake is washed with 50 mL of a solvent mixture comprising acetonitrile and water (1:1, v/v). The wet cake is dried at 20-25 °C on air till constant weight. 8.45 g, 89.9 percent, of [R-(R*, R*)]-2-(4-fluorophenyl)-ss;, No.- dihydroxy-5-(l-methylethyl)-3-phenyl-4-[(phenylamino)- carbonyl]-lH-pyrrole-l-heptanoic acid tertiary butyl ester (II) is isolated having a melting range of 142-145 °C. The pu- rity of the obtained product is higher than 99 percent.110.0 grams of (4R-cis)-1 , 1-dimethylethyl-6[2[-(4-fluorophenyl]-5-(1- methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1yl]ethyl]-2, 2- dimethyl-1, 3-dioxane-4-acetate was dissolved in 1100 ml of acetonitrile at 30- 35

An impurity arising in the synthesis of Atorvastatin

Molecular Weight:614.7
XLogP3:6.3
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:14
Exact Mass:614.31560064
Monoisotopic Mass:614.31560064
Topological Polar Surface Area:101
Heavy Atom Count:45
Complexity:920
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes