(S)-2,2,2-trifluoro-N-(6-methoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide → tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate

HRID 501736

Reaktionsgleichung

Reaktionsgleichung von HRID 501736
FC(F)(F)C(N[C@@H]1C2C(=CC=C(OC)C=2)C(=O)C1)=O.[CH2:20]([O:23][C@H:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][CH:34]([CH3:36])[CH3:35])=[CH:30][CH:31]=2)[C@@H:26]([NH2:37])[CH2:25]1)[CH:21]=[CH2:22].[C:38]([O:42][C:43](=[O:56])[NH:44][C@H:45]([CH:53]1[CH2:55][O:54]1)[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)([CH3:41])([CH3:40])[CH3:39].Cl([O-])(=O)(=O)=O.[Li+].[Cl-].[Na+].O.C([O-])(O)=O.[Na+]>CC#N>[CH2:20]([O:23][C@H:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][CH:34]([CH3:35])[CH3:36])=[CH:30][CH:31]=2)[C@@H:26]([NH:37][CH2:55][C@@H:53]([OH:54])[C@@H:45]([NH:44][C:43](=[O:56])[O:42][C:38]([CH3:40])([CH3:39])[CH3:41])[CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:25]1)[CH:21]=[CH2:22]

Komponenten

7

Edukt 5

HCID 1472787(S)-2,2,2-trifluoro-N-(6-methoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamideHCID 9816717tert-butyl ((1S)-1-(oxiran-2-yl)-2-phenylethyl)carbamateHCID 23665649Lithium perchlorateHCID 59423754(1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-amineHCID 129703874Sodium hydrogencarbonate brine

Produkt 1

HCID 86622357tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamateAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

Step AW (1): A solution of (1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-amine (1.3 g, 5.3 mmol), (S)-(1-oxiranyl-2-phenylethyl)-carbamic acid tert-butyl ester (1.7 g, 6.5 mmol), and lithium perchlorate (2.8 g, 26.3 mmol) in 40 mL CH3CN was stirred at 50° C. for 18 h. The mixture was poured into brine/NaHCO3 solution, extracted with EtOAc (200 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified using silica-gel column chromatography (30-80% EtOAc/Hexane) to afford 1.2 g (45% yield) of tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate. LC-MS (M+H)+=511.25. 1H NMR (300 MHz, CDCl3) δ 1.2-1.4 (m, 15H) 2.5-2.7 (m, 1H) 2.7-2.9 (m, 2H) 3.0-3.1 (m, 2H) 3.5-3.7 (m, 1H) 3.7-3.9 (m, 1H) 4.0-4.1 (m, 2H) 4.2-4.3 (m, 1H) 4.5-4.7 (m, 2H) 4.7-4.8 (m, 1H) 5.1-5.3 (m, 2H) 5.8-6.0 (m, 1H) 6.8-6.9 (m, 1H) 7.0-7.3 (m, 7H).

Aufarbeitung

  1. extractionextracted with EtOAc (200 mL×2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-c42dcc9c8d88439cbcd20d583af29ab2
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772221B2

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