Atorvastatin lactone Chemical Properties

Melting point:

103-106°C

alpha 

D +26.05° (c = 1 in chloroform)

Boiling point:

674.8±55.0 °C(Predicted)

Density 

1.24±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,2-8°C

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

pka

13.39±0.40(Predicted)

form 

Solid

color 

White to Light Yellow

optical activity

Consistent with structure

Merck 

14,864

Safety Information

HS Code 

2933.99.7500

Atorvastatin lactone Usage And Synthesis

Chemical Properties

Slightly Yellow Solid

Uses

Atorvastatin intermediate as inhibitor of MAP kinase and/or HMG-CoA reductase for the treatment of inflammation

Uses

Atorvastatin Lactone (Atorvastatin EP Impurity H) is an intermediate of Atorvastatin, a inhibitor of MAP kinase and/or HMG-CoA reductase for the treatment of inflammation.

Synthesis

Calcium salt of (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid (500 mg, 0.413 mmol) was used as a raw material, which was suspended in water (8 mL), EtOAc (4 mL) was added, and the mixture was cooled in an ice bath (4°C). An aqueous 0.2 M HCl solution (4.55 mL, 0.910 mmol) was added slowly and dropwise under vigorous stirring until a clarified solution was formed. The reaction mixture was gradually warmed to room temperature, followed by separation of the organic and aqueous layers. The aqueous layer was extracted with EtOAc (3 x 5 mL), the combined organic layers were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting foam (469 mg) was dissolved in toluene (20 mL) and the mixture was heated to 0°C and refluxed for 2.5 h under a Dean-Stark apparatus. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. Purification by fast column chromatography (eluent: heptane/EtOAc, gradient from 1:3 to 1:5) afforded the target product 5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1H-pyrrole-3-carboxamide (394 mg. (white foamy substance). NMR hydrogen spectrum (400 MHz, CDCl3) δ 7.24-7.10 (m, 9H), 7.09-6.96 (m, 5H), 6.92-6.82 (br s, 1H), 4.57-4.47 (m, 1H), 4.34-4.27 (m, 1H), 4.27-4.16 (m, 1H), 4.09-3.97 (m , 1H), 3.62-3.47 (m, 1H), 2.66 (ABdd, J = 17.7, 4.8 Hz, 1H), 2.55 (ABddd, J = 17.7, 3.4, 1.5 Hz, 1H), 2.11 (d, J = 2.9 Hz, 1H), 1.95-1.82 (m, 1H), 1.81-1.67 (m, 2H) , 1.63-1.57 (m, 1H), 1.56-1.45 (m, 6H).

References

[1] Patent: WO2017/137469, 2017, A1. Location in patent: Page/Page column 62
[2] Patent: CN105085497, 2017, B. Location in patent: Paragraph 0115; 0116; 0117

Atorvastatin lactone(125995-03-1)Related Product Information

• Phenyl salicylate
• Diphenyl ether
• Polyvinylpyrrolidone
• Atorvastatin calcium
• Isopropyl alcohol
• N-Methyl-2-pyrrolidone
• Pyrrolidine
• PHENYL VALERATE
• ISOPROPYL LAURATE
• N-Vinyl-2-pyrrolidone
• TRIOXSALEN
• Atorvastatin
• tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate
• Defluoro Atorvastatin
• Atorvastatin Impurity 40
• PHENYL RESIN
• Phenylacetic acid
• 3S,5R isoMer, or (3S,5R)-7-[3-(phenylcarbaMoyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid calciuM salt