1,3-Dichloroacetone → 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole

Participants

Reaction Conditions

Reaction Steps

(E)-3-(4-(Trifluoromethyl)phenyl)-2-propenamide (20.0 g, 92.9 mmol) was added to toluene (75 ml), and 1,3-dichloroacetone (22.0 g, 173.3 mmol) and toluene (25 ml) were added. The mixture was subjected to refluxing azeotropic dehydration for 9 hours. The reaction mixture was divided into two equal portions and one of them was concentrated under reduced pressure. To the residue were added dimethyl sulfoxide (100 ml), sodium acetate trihydrate (15.9 g, 116.8 mmol) and water (20 ml). The mixture was stirred at 70-75° C. for 4.5 hours. 2N-Aqueous sodium hydroxide solution (60 ml) was added at the same temperature and the mixture was stirred for 1 hour. After allowing to cool to room temperature, toluene (400 ml) and water (400 ml) were added and the mixture was partitioned. After washing with 5% brine (200 ml), the organic layer was concentrated under reduced pressure. To the residue was added methanol (10 ml) and the mixture was heated to 60° C. to allow dissolution. After allowing to cool to room temperature and stirring, the mixture was stirred for 1 hour under ice-cooling. The precipitated crystals were collected by filtration, washed with cold-methanol (5 ml) and dried under reduced pressure to give 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]-1,3-oxazole (5.96 g, 22.1 mmol, yield 48%).

Provenance & Evidence