Trifluoroacetic acid → (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylic acid 4-trifluoromethoxybenzylamide

Participants

Reaction Steps

Tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]-piperazine-1-carboxylate prepared in Example 148 (120 mg, 0.26 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, then added methylene chloride (2 ml) and triethylamine (2 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure. The residue was dissolved in DMF (10 ml). To the solution, a mixture of 4-trifluoromethoxybenzylamine (125 mg, 0.65 mmol) and 1,1′-carbonyldiimidazole (110 mg, 0.68 mmol) in DMF (5 ml) stirred at room temperature for 3 hours was added followed by stirring at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylic acid 4-trifluoromethoxybenzylamide (48 mg, yield 32%) as a white powder.

Provenance & Evidence