Dimethylformamide → 3-Fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde

HRID 1897585Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1897585
[Li][CH2:2][CH2:3][CH2:4][CH3:5].C(N[CH:10]([CH3:12])[CH3:11])(C)C.Br[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([F:20])[CH:19]=1.CN([CH:24]=[O:25])C.[C:26]([O-:29])(O)=[O:27].[Na+]>C1COCC1>[F:20][C:18]1[CH:17]=[N:16][CH:15]=[C:14]([C:5]2[CH:4]=[C:3]3[C:12](=[CH:10][CH:11]=2)[C:26](=[O:27])[O:29][CH2:2]3)[C:19]=1[CH:24]=[O:25]

Komponenten

7

Edukt 5

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 516892Sodium BicarbonateHCID 8202063-Bromo-5-fluoropyridineHCID 178418339Butyllithium

Produkt 1

HCID 866748373-Fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

n-BuLi (13.85 mL, 22.16 mmol) was added to a solution of diisopropylamine (3.16 mL, 22.16 mmol) in THF (50 mL) at −78° C. After 30 min, 3-bromo-5-fluoropyridine (3.0 g, 17.05 mmol) in THF (25 mL) was added dropwise. The mixture was stirred for 1 hr, and then DMF (3.96 mL, 51.1 mmol) was added dropwise. Saturated aqueous NaHCO3 was added and the cooling bath was removed. The mixture was shaken with ethyl acetate and the organic phase was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel flash chromatography employing dichloromethane-methanol, 9:1 to give 3-fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.81 (d, J=1.4 Hz, 1H), 8.83 (s, 1H), 10.17 (s, 1H)

Aufarbeitung

  1. customthe cooling bath was removed
  2. stirringThe mixture was shaken with ethyl acetate
  3. washthe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e094975e23ec4295983ec8e9febc6db8
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08519134B2

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