Trifluoroacetic acid → (S)-2-methyl-6-nitro-2-[4-{1-[3-(4-trifluoromethoxyphenyl)-2-propenyl]piperidin-4-yl}piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole

Participants

Reaction Steps

Tert-butyl (S)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]piperidine-1-carboxylate (750 mg, 1.66 mmol) was dissolved in methylene chloride (5 ml), trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 1.5 hours. The reaction mixture was concentrated. To the residue, methylene chloride (5 ml) and triethylamine (5 ml) were added, and the mixture was stirred at room temperature for 10 minutes and then concentrated. The residue was dissolved in 1,2-dichloroethane (20 ml), 3-(4-trifluoromethoxyphenyl)propenal (396 mg, 1.83 mmol) and sodium triacetoxyborohydride (564 mg, 2.66 mmol) were added followed by stirring at room temperature for 3.5 hours. The reaction solution was washed with a saturated sodium hydrogencarbonate solution (15 ml), water (20 ml), and a saturated saline solution (20 ml) in this order, and then dried over sodium sulfate. After filtration, the filtrate was concentrated, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1) and then recrystallized from methanol/water to obtain (S)-2-methyl-6-nitro-2-[4-{1-[3-(4-trifluoromethoxyphenyl)-2-propenyl]piperidin-4-yl}piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole (446 mg, 49%) as a light yellow powder.

Provenance & Evidence