Tetrahydrofuran → Atorvastatin lactone

HRID 360035

반응식

HRID 360035 반응식
[NH2:1][CH2:2][CH2:3][C@H:4]1OC(C)(C)[O:7][C@@H:6]([CH2:12][C:13]([O:15]C(C)(C)C)=[O:14])[CH2:5]1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27](=O)[CH:28]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:29]([C:39](=O)[CH:40]([CH3:42])[CH3:41])[C:30]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:31])=[CH:23][CH:22]=1.O1CCCC1.[Cl-].[NH4+]>CCCCCCC.C1(C)C=CC=CC=1.O>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[N:1]([CH2:2][CH2:3][C@@H:4]3[CH2:5][C@@H:6]([OH:7])[CH2:12][C:13](=[O:14])[O:15]3)[C:39]([CH:40]([CH3:42])[CH3:41])=[C:29]([C:30]([NH:32][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[O:31])[C:28]=2[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[CH:25][CH:26]=1

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 2734288(4R,6R)-tert-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetateHCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamide

생성물 1

HCID 6483036Atorvastatin lactone

시약·촉매·용매 2

HCID 962Water용매HCID 22263336Toluene heptane용매

실험 절차

A solution of (4R-cis)-1,1-dimethylethyl 6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate, 2.56 g (9.36 mol), and (±)-4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutaneamide mixture of R-(R*,R*)], [R-(R*,S*)], [S-(R*,R*)]and [S-(R*,S*)]isomers, 3.00 g (7.20 mol), in 60 mL of heptane:toluene (9:1) is heated at reflux for 24 hours. The solution is cooled and poured into 300 mL of tetrahydrofuran and 150 mL of saturated ammonium chloride in water. The layers are separated and the organic layer is added to 15 mL of 10% hydrochloric acid solution 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-4hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1H-pyrrole-3carboxamide (2.92 g) is isolated in two crops.

후처리

  1. temperatureat reflux for 24 hours
  2. temperatureThe solution is cooled
  3. customThe layers are separated
  4. additionthe organic layer is added to 15 mL of 10% hydrochloric acid solution
  5. additionTo this solution is added sodium hydroxide (3.6 g)
  6. stirringthe mixture is stirred for 30 hours
  7. additionby adding 150 mL of water, 90 mL of hexane
  8. customseparating the layers
  9. stirringstirred for three hours
  10. extractionextracted with 150 mL of ethyl acetate
  11. additionA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
  12. waitto stand 18 hours
  13. concentrationThe solution is concentrated in vacuo
  14. dissolutionthe concentrate is redissolved in 50 mL of ethyl acetate
  15. additiontreated with one drop of concentrated hydrochloric acid
  16. stirringThe solution is stirred two hours
  17. concentrationconcentrated in vacuo
  18. dissolutiondissolved in 3.0 mL of toluene

출처 및 근거

ORD 기록
ord-595385ec776e4120a6b9e428861bb1f3
출처 데이터셋
uspto-grants-1991_03
특허 번호
US05003080

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