Sodium hydride → N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine

HRID 609686Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 609686
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[NH:18][CH:17]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:26][Si:27]([CH3:35])([CH3:34])[CH2:28][CH2:29][S:30](Cl)(=[O:32])=[O:31]>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[N:18]([S:30]([CH2:29][CH2:28][Si:27]([CH3:35])([CH3:34])[CH3:26])(=[O:32])=[O:31])[CH:17]=2)[CH2:14][CH2:15]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 98370862-(Trimethylsilyl)ethane-1-sulfonyl chlorideHCID 227144175-fluoro-3-(1-tert-butoxycarbonylpiperidin-4-yl)-1H-indole

Produkt 1

HCID 22615698N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidineAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Sodium hydride (96 mg, 4.07 mmol) was added to a solution of N-tert-butoxycarbonyl-4-(5-fluoroindol-3-yl)piperidine (1.28 g, 4.07 mmol), [prepared as described in Step 1, above] in DMF (6 ml) at 0° C. and the reaction mixture was stirred for 30 min. 2-Trimethylsilylethanesulfonyl chloride (820 mg, 4.07 mmol) was added and the reaction mixture was slowly warmed to RT over 30 min. After 2.5 h, the reaction mixture was quenched with water (10 ml) and the product was extracted into methylene chloride. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Due to incomplete reaction the above steps were repeated on the isolated crude reaction mixture. The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes) to afford N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine (84%) as a clear oil.

Aufarbeitung

  1. waitAfter 2.5 h
  2. customthe reaction mixture was quenched with water (10 ml)
  3. extractionthe product was extracted into methylene chloride
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customDue to incomplete reaction the above steps
  7. customisolated crude
  8. customreaction mixture
  9. customThe final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-eb9f8a59b9a0471693d5485b5457d74d
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US05998412

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