5-Bromo-2-fluorobenzaldehyde → 2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine

HRID 335955Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 335955
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([F:14])[C:3]=1[O:15][CH2:16][O:17][CH3:18].C([Li])CCC.BrC1C=CC(F)=C(C=1)C=O>O1CCCC1>[F:14][C:4]1[C:3]([O:15][CH2:16][O:17][CH3:18])=[CH:2][CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[N:5]=1

Komponenten

5

Edukt 3

HCID 7363275-Bromo-2-fluorobenzaldehydeHCID 673828784-Bromo-2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridineHCID 178418339Butyllithium

Produkt 1

HCID 673830702-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridineAusbeute 12,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

4-Bromo-2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine (1.62 g, 5.06 mmol) was dissolved in dry tetrahydrofuran (50 mL) under nitrogen and cooled in a dry ice bath. Butyllithium solution (2.5 M in hexanes, 2.2 mL, 5.50 mmol) was added and the reaction stirred for 5 min. A solution of 5-bromo-2-fluorobenzaldehyde (1.03 g, 5.06 mmol) in dry THF (10 mL) was added and the reaction stirred for 35 min then quenched by addition of saturated ammonium chloride (20 mL). Water (100 mL) and EtOAc (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to EtOAc gradient) gave recovered starting material (0.30 g, 18%), debrominated 2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine (0.15 g, 0.61 mmol, 12.0% yield) and the desired (5-bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)methanol (0.85 g, 1.90 mmol)

Aufarbeitung

  1. temperaturecooled in a dry ice bath
  2. stirringthe reaction stirred for 35 min
  3. customthen quenched by addition of saturated ammonium chloride (20 mL)
  4. additionWater (100 mL) and EtOAc (100 mL) were added
  5. additionthe phases mixed
  6. customseparated
  7. dry with materialThe organic was dried with magnesium sulfate
  8. customevaporated to dryness under reduced pressure
  9. customPurification
  10. customgave
  11. customrecovered

Quellen und Nachweise

ORD-Eintrag
ord-89505d091e214be59aeacf602664c79f
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883782B2

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