4-Methoxybenzyl alcohol → 2-(4-Methoxybenzyloxy)-3-bromo-4-methylpyridine

HRID 632828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632828
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][OH:10])=[CH:7][CH:6]=1.[Br:13][C:14]1[C:15](Cl)=[N:16][CH:17]=[CH:18][C:19]=1[CH3:20]>C1COCC1>[Br:13][C:14]1[C:15]([O:10][CH2:9][C:8]2[CH:11]=[CH:12][C:5]([O:4][CH3:3])=[CH:6][CH:7]=2)=[N:16][CH:17]=[CH:18][C:19]=1[CH3:20]

Komponenten

5

Edukt 3

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 404251193-Bromo-2-chloro-4-methylpyridine

Produkt 1

HCID 670001042-(4-Methoxybenzyloxy)-3-bromo-4-methylpyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

3-bromo-2-(4-methoxybenzyloxy)-4-methylpyridine was prepared by the procedure described in J. Med. Chem., 2008, 51, 3065. A pressure vessel was charged with anhydrous THF (25 ml) and sodium hydride (1.44 g, 36.18 mmol, 60% dispersion). To this stirred mixture was added portionwise a solution of 4-methoxybenzyl alcohol (5.0 g, 36.18 mmol) in anhydrous THF (15 ml). After addition was complete, the mixture was stirred at room temperature for 30 minutes and a solution of 3-bromo-2-chloro-4-picoline (4.97 g, 24.08 mmol) in anhydrous THF (15 ml) was added. The vessel was sealed and the reaction mixture was heated at 75° C. for 6 hours. Upon cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and water. The separated organic layer was washed with water, sat'd NaCl(aq.), dried over MgSO4, filtered, and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 4:1 hexanes: EtOAc) gave the title compound as a clear oil which crystallized on standing (6.71 g, 90%).

Aufarbeitung

  1. custom3-bromo-2-(4-methoxybenzyloxy)-4-methylpyridine was prepared by the procedure
  2. additionAfter addition
  3. customThe vessel was sealed
  4. temperaturethe reaction mixture was heated at 75° C. for 6 hours
  5. temperatureUpon cooling to room temperature
  6. customthe reaction mixture was partitioned between ethyl acetate and water
  7. washThe separated organic layer was washed with water, sat'd NaCl(aq.)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. washElution through a flash column (silica gel 60, 230-400 mesh, 4:1 hexanes: EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-ddd89b6405604c1d82aa56acf8fd2abf
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321766B1

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