Ammonium Hydroxide → Oxazole

Participants

Reaction Steps

To a stirred mixture of cupric bromide (2.27 g, 10.2 mmol) in 15 mL of ethyl acetate under argon at room temperature was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (3.04 mL, 20.3 mmol). The mixture was stirred at room temperature for 30 minutes, at which time a solution of oxazoline D (2.63 g, 4.84 mmol) in 15 mL of chloroform was added. The mixture was stirred at room temperature for 17 hours and another batch of cupric bromide (2.27 g, 10.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.52 mL, 10.2 mmol) was added. The mixture was stirred at room temperature for 6 hours and cupric bromide (2.27 g, 10.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.52 mL, 10.2 mmol) were added. The mixture was stirred at room temperature for 19 hours, at which time again cupric bromide (2.27 g, 10.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.52 mL, 10.2 mmol) were added. The mixture was stirred at room temperature for 6 hours and a last batch of cupric bromide (2.27 g, 10.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.52 mL, 10.2 mmol) was added. The reaction mixture was stirred at room temperature for 17 hours and then poured into a mixture of 400 mL of ethyl acetate and 360 mL of a solution of 1:1 concentrated ammonium hydroxide solution and saturated ammonium chloride solution. The aqueous layer was separated and extracted with ethyl acetate (2×400 mL). The combined ethyl acetate extracts were dried (magnesium sulfate), filtered and concentrated in vacuo. Purification was effected by flash chromatography on 240 g of Merck silica gel 60 using 15% acetone in toluene as eluant to give 0.77 g (29%) of oxazole E and 0.43 g (16%) of recovered oxazoline D.

Provenance & Evidence