Sodium Hydroxide → Mubritinib

Participants

Reaction Steps

The obtained 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (1.00 g, 3.71 mmol) and diisopropylethylamine (0.95 mL, 5.44 mmol) were added to THF (tetrahydrofuran) (15 ml). Methanesulfonyl chloride (0.45 mL, 5.81 mmol) was added dropwise under ice-cooling. The mixture was stirred at the same temperature for 1 hour. 4-[4-(1H-1,2,3-Triazol-1-yl)butyl]phenol (900 mg, 4.14 mmol) and tetra(n-butyl)ammonium bromide (60 mg, 0.19 mmol) were added at the same temperature. A 2N aquous sodium hydroxide solution (7.5 mL, 15.0 mmol) was added dropwise at not more than 15° C. and the mixture was stirred with reflux for 1 hour. After allowing to cool to room temperature and stirring, the organic layer was concentrated under reduced pressure. Ethanol (20 ml) was added to the residue, and the mixture was stirred with reflux. Water (20 ml) was added dropwise at the same temperature. After allowing to cool to room temperature and stirring, the mixture was ice-cooled. The precipitated crystals were collected by filtration, washed with water (20 ml) 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 (1.61 g, 3.44 mmol, yield 88%).

Provenance & Evidence