1,2-Dichloroethane → Methyl 4-oxo-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 80 mg, 0.195 mmol), 5-(2-hydroxyethyl)-3,4-dimethylthiazolium iodide (11.12 mg, 0.039 mmol), 1,2-dichloroethane (1 mL), EtOH (1.000 mL), triethylamine (0.082 mL, 0.585 mmol) and methyl acrylate (0.053 mL, 0.585 mmol) was bubbled with nitrogen for 1 min. and then sealed in a 1-dram vial. The mixture was heated at 75° C. for 15 h. Additional 5-(2-hydroxyethyl)-3,4-dimethylthiazolium iodide (30 mg) and methyl acrylate (0.053 mL, 0.585 mmol) were added and the mixture was stirred at 75° C. for 7 h. The solvents were removed under reduced pressure. The residue was treated with water (2 mL) and extracted with dichloromethane. The combined dichloromethane extracts were dried (sodium sulfate) and concentrated. Flash chromatography purification (4 g silica gel column, 20→100% dichloromethane in heptanes) afforded methyl 4-oxo-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (23 mg, 0.046 mmol, 23.76% yield) as a glassy solid.

Provenance & Evidence