Hydrochloric Acid → Atorvastatin lactone

HRID 466297

Reaction equation

HRID 466297 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

HCID 6483036Atorvastatin lactone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

(4R-Cis)-1,1-dimethylethyl 6-[2[2-(4-fluoro-phenyl)-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 mmol), 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 3 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 2 hours, concentrated in vacuo, and dissolved in 3.0 mL of toluene. (2R-Trans)-5-(4-fluorophenyl)-2-(1-methyl -ethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo -2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide (3.01 g) is isolated in two crops.

Workup

  1. stirringthe mixture is stirred for 30 hours
  2. customseparating the layers
  3. stirringstirred for 3 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 2 hours
  11. concentrationconcentrated in vacuo
  12. dissolutiondissolved in 3.0 mL of toluene

Sources & evidence

ORD record
ord-6b475ef4f24c47b39d622ca1758d9e9c
Source dataset
uspto-grants-1992_10
Patent number
US05155251

Linked notes

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