Water → 4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehyde

HRID 595927Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595927
Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[O:9]1[CH2:14][CH2:13][CH:12]([CH:15]=[O:16])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+].O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:8][C:5]1[N:6]=[CH:7][C:2]([C:12]2([CH:15]=[O:16])[CH2:13][CH2:14][O:9][CH2:10][CH2:11]2)=[CH:3][CH:4]=1

Komponenten

8

Edukt 5

HCID 962WaterHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27831685-Bromo-2-fluoropyridineHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehyde

Produkt 1

HCID 1180452994-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehydeAusbeute 23,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a solution of 5-bromo-2-fluoropyridine (2.0 g, 11.36 mmol) in dioxane (35 mL) was added tetrahydro-2H-pyran-4-carbaldehyde (2.59 g, 22.73 mmol), Pd(OAc)2 (0.25 g, 1.14 mmol), cesium carbonate (7.41 g, 22.73 mmol), and water (10.24 μL, 0.57 mmol), xantphos (0.98 g, 1.70 mmol). The mixture was purged with nitrogen for 5 min, the resulting mixture was heated to 110° C. in an oil bath for 15 h. The mixture was diluted with ethyl acetate, and was washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography on silicagel (ISCO) eluting with 0-80% ethyl acetate in heptane to give 4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehyde (560 mg, 2.68 mmol, 23.5% yield) as red color oil. LCMS (m/z): 210 (MH+), 0.45 min.

Aufarbeitung

  1. customThe mixture was purged with nitrogen for 5 min
  2. additionThe mixture was diluted with ethyl acetate
  3. washwas washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silicagel (ISCO)
  7. washeluting with 0-80% ethyl acetate in heptane

Quellen und Nachweise

ORD-Eintrag
ord-2c6ae76b0a164bd7a2b44de56cc7a056
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242996B2

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