反应详情

The obtained 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (567 g, 2.11 mol) and diisopropylethylamine (340 g, 2.63 mol) were added to THF (3.4 L). A solution of methanesulfonyl chloride (302 g, 2.63 mol) in THF (567 ml) was added dropwise under ice-cooling. The mixture was stirred at the same temperature for 1 hour and diisopropylethylamine (27.3 g, 0.21 mol), methanesulfonyl chloride (24.2 g, 0.21 mol) and THF (57 ml) solution were added. The mixture was stirred under reflux for 1.5 hours. After allowing to cool to room temperature, 15% aqueous sodium hydroxide (1.96 kg, 7.35 mol) was added dropwise. 4-[4-(1H-1,2,3-Triazol-1-yl)butyl]phenol (503 g, 2.32 mol) and tetra(n-butyl) ammonium bromide (68.0 g, 0.21 mol) were added at the same temperature, and the mixture was refluxed for 4 hours under stirring. Water (3.1 L) and methanol (7.4 L) were added dropwise at the same temperature. After allowing to cool to room temperature, the mixture was stirred at the same temperature for 1 hour. The precipitated crystals were collected by filtration, washed with THF/methanol/water (1:1:2) (2.8 L), water (2.8 L) and cold-methanol (2.8 L) and dried under reduced pressure to give 1-[4-[4-[[2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazol-4-yl]methoxy]phenyl]butyl]-1H-1,2,3-triazole (883 g, 1.88 mol, yield 85%).

1. temperaturecooling
2. stirringThe mixture was stirred
3. temperatureunder reflux for 1.5 hours
4. temperaturethe mixture was refluxed for 4 hours
5. stirringunder stirring
6. temperatureto cool to room temperature
7. stirringthe mixture was stirred at the same temperature for 1 hour
8. filtrationThe precipitated crystals were collected by filtration
9. washwashed with THF/methanol/water (1:1:2) (2.8 L), water (2.8 L)
10. dry with materialcold-methanol (2.8 L) and dried under reduced pressure