Potassium Hydroxide → 6-Fluoro-4-iodo-N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)pyridin-3-amine

HRID 1640908Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1640908
OC(C(F)(F)F)=O.[F:8][C:9]1[N:14]=[CH:13][C:12]([NH2:15])=[C:11]([I:16])[CH:10]=1.Br[CH2:18][CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.[OH-].[K+].[F-].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[F:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][CH2:18][CH2:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:11]([I:16])[CH:10]=1

Komponenten

7

Edukt 4

HCID 14797Potassium HydroxideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 522689Potassium FluorideHCID 866418746-fluoro-4-iodopyridin-3-amine TFA salt

Produkt 1

HCID 667381816-Fluoro-4-iodo-N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)pyridin-3-amineAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Mix 6-fluoro-4-iodopyridin-3-amine TFA salt (0.36 g, 1.50 mmol), 2-[(2-bromoethyl)oxy]tetrahydro-2H-pyran (1.38 g, 6.60 mmol), potassium hydroxide (0.19 g, 3.30 mmol), potassium fluoride (0.19 g, 3.30 mmol), and tetrabutylammonium iodide (0.11 g, 0.3 mmol) in 1,4-dioxane (1.5 mL) in a seal reactor. Heat the reaction mixture at 100° C. overnight. Cool the reaction mixture to RT. Quench with water. Extract with ethyl acetate, wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4. After filtration, concentrate and purify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2) to give the title compound (0.36 g, 66%) with 100% HPLC purity. MS (ES) m/z 367 [M+1]+.

Aufarbeitung

  1. temperatureCool the reaction mixture to RT
  2. customQuench with water
  3. extractionExtract with ethyl acetate
  4. washwash the organic layer with water and saturated aqueous sodium chloride
  5. dry with materialDry over MgSO4
  6. filtrationAfter filtration
  7. concentrationconcentrate
  8. custompurify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-f070a66297674ab3b0d16f512f3a6f97
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08114872B2

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