Hydrochloric Acid → N-(3-(trifluoromethyl)-1,2-oxazol-5-yl)acetamide

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Reaction Steps

Dry benzene (56 ml) and pyridine (11.85 g, 150 mmole) were added to 3-trifluoromethyl-5-aminoisoxazole (9.12 g, 60.0 mmole) and the mixture was cooled. Acetyl chloride (10.37 g, 132 mmole) was added dropwise to the mixture, while keeping it below 10° C. After being added dropwise, the mixture was stirred with ice cooling for 10 minutes and at room temperature for 1 hour. Water (60 ml) was added and it was stirred for an additional hour. Benzene (60 ml) was added and the mixture was separated. The benzene layer was washed successively with 2% hydrochloric acid (60 ml) and a 8% solution of sodium bicarbonate and the solvent was evaporated under reduced presssure. Methanol (120 ml) and sodium hydroxide (4.80 g 120 mmole) were added to the residue and the mixture was stirred overnight at room temperature. After being neutralized with conc. hydrochloric acid, the solvent was evaporated under reduced pressure and the resulting residue was dissolved by the addition of benzene (100 ml) and ethyl acetate (20 ml). This solution was washed with water (60 ml) and the solvents were evaporated under reduced pressure to give 3-trifluoromethyl-5-acetylaminoisoxazole (9.51 g) as crystals. This product was recrystallized from benzene to give colorless plates. Yield: 5.67 g, m.p. 108.5°-109.5° C.

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