Reaktion #720010

Reaktionsgleichung

3-bromo-2-chloro-4-picoline

4-methoxybenzyl alcohol

sodium hydride

→

title compound

3-Bromo-2-(4-methoxybenzyloxy)-4-methylpyridine

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige3-bromo-2-(4-methoxybenzyloxy)-4-methylpyridine was prepared by the procedure
2. 2
   workup.ADDITIONAfter addition
3. 3
   SonstigeThe vessel was sealed
4. 4
   Temperaturthe reaction mixture was heated at 75° C. for 6 hours
5. 5
   TemperaturUpon cooling to room temperature
6. 6
   Sonstigethe reaction mixture was partitioned between ethyl acetate and water
7. 7
   WaschenThe separated organic layer was washed with water, sat'd NaCl(aq.)
8. 8
   Trocknendried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    WaschenElution through a flash column (silica gel 60, 230-400 mesh, 4:1 hexanes: EtOAc)

Vorschrift

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%).

Quelle