Sodium hydride → 5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole

HRID 1926750Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1926750
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].Cl[CH2:14][C:15]1[C:16]([F:21])=[N:17][CH:18]=[CH:19][CH:20]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:14][C:15]1[C:16]([F:21])=[N:17][CH:18]=[CH:19][CH:20]=1)[CH:6]=[CH:5]2

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 871105-ChloroindoleHCID 226413043-(Chloromethyl)-2-fluoropyridine

Produkt 1

HCID 577430625-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indoleAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

In a 50 ml, three-necked flask fitted with a magnetic stirrer under inert atmosphere, 5-chloro-1H-indole x70 (1.13 g, 7.43 mmol) is dissolved in dry DMF (20 ml). At 0° C., NaH (327 mg, 8.18 mmol, 60% in mineral oil) is added and the mixture is stirred at this temperature for 0.3 h. A solution of 3-(chloromethyl)-2-fluoropyridine x71 (obtained from (2-fluoropyridin-3-yl)methanol and SOCl2 (1.3 g, 8.92 mmol)) in DMF (5 ml) is then added and stirring is continued for 0.5 h at 0° C. The reaction mixture is poured on ice and the aqueous phase is extracted three times with AcOEt. The combined organic phases are dried over MgSO4, filtered and concentrated. Purification by chromatography on silicagel (Hexane/AcOEt:9/1 (v/v)) affords 5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole x72 as a solid (1.13 g).

Aufarbeitung

  1. stirringstirring
  2. waitis continued for 0.5 h at 0° C
  3. additionThe reaction mixture is poured on ice
  4. extractionthe aqueous phase is extracted three times with AcOEt
  5. dry with materialThe combined organic phases are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by chromatography on silicagel (Hexane/AcOEt:9/1 (v/v))

Quellen und Nachweise

ORD-Eintrag
ord-c2a11e7ff3e947e49aa5a31f439daa83
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08183241B2

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