Hydrochloric Acid → Atorvastatin lactone

HRID 1587176

Reaktionsgleichung

Reaktionsgleichung von HRID 1587176
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:31][CH2:32][C@H:33]3OC(C)(C)[O:36][C@@H:35]([CH2:41][C:42]([O:44]C(C)(C)C)=[O:43])[CH2:34]3)[C:10]([CH:28]([CH3:30])[CH3:29])=[C:11]([C:19]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:20])[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.Cl.[OH-].[Na+].O>O1CCCC1.CCCCCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:31][CH2:32][C@@H:33]3[CH2:34][C@@H:35]([OH:36])[CH2:41][C:42](=[O:43])[O:44]3)[C:10]([CH:28]([CH3:29])[CH3:30])=[C:11]([C:19]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:20])[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 10168503Atorvastatin Acetonide tert-Butyl Ester

Produkt 1

HCID 6483036Atorvastatin lactone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8058HexaneLösungsmittel

Versuchsvorschrift

(4R-cis)-1,1-dimethylethyl 6-[2[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4-acetate, 4.37 g (6.68 mol), is dissolved in 200 mL of tetrahydrofuran and 15 mL of 10% hydrochloric acid solution is added, and the solution is stirred for 15 hours. To this solution is added sodium hydroxide (3.6 g) and the mixture is stirred for 30 hours. The reaction is stopped by adding 150 mL of water, 90 mL of hexane, and separating the layers. The aqueous layer is acidified with dilute hydrochloric acid solution, stirred for three hours and extracted with 150 mL of ethyl acetate. A drop of concentrated hydrochloric acid is added to the ethyl acetate solution and the solution is allowed to stand 18 hours. The solution is concentrated in vacuo and the concentrate is redissolved in 50 mL of ethyl acetate and treated with one drop of concentrated hydrochloric acid. The solution is stirred two hours, concentrated in vacuo, and dissolved in 3.0 mL of toluene. (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide (3.01 g) is isolated in two crops.

Aufarbeitung

  1. stirringthe mixture is stirred for 30 hours
  2. customseparating the layers
  3. stirringstirred for three hours
  4. extractionextracted with 150 mL of ethyl acetate
  5. additionA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
  6. waitto stand 18 hours
  7. concentrationThe solution is concentrated in vacuo
  8. dissolutionthe concentrate is redissolved in 50 mL of ethyl acetate
  9. additiontreated with one drop of concentrated hydrochloric acid
  10. stirringThe solution is stirred two hours
  11. concentrationconcentrated in vacuo
  12. dissolutiondissolved in 3.0 mL of toluene

Quellen und Nachweise

ORD-Eintrag
ord-28d4d419e49047a6b838a874c9a26f38
Quelldatensatz
uspto-grants-1993_06
Patentnummer
US05216174

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