Trifluoroacetic acid → 4-[(2,3-Dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4'-piperidin]-1'-yl)-2-oxoethyl]piperazine-1-carboxylic acid (4-trifluoromethylphenyl)amide

Participants

Reaction Steps

Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidine]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate prepared in Example 653 (300 mg, 0.67 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure. To the solution, methylene chloride (1 ml) and triethylamine (1 ml) were added followed by stirring at room temperature for 5 minutes. The solution was concentrated under reduced pressure, and the residue was dissolved in DMF (10 ml). To the solution, a mixture of 4-aminobenzotrifluoride (0.17 ml, 1.33 mmol) and 1,1′-carbonyldiimidazole (220 mg, 1.33 mmol) and DMF (5 ml) stirred at room temperature for 3 hours was added followed by stirring at room temperature for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate, and 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, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford 4-[(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidin]-1′-yl)-2-oxoethyl]piperazine-1-carboxylic acid (4-trifluoromethylphenyl)amide (213 mg, yield 59%) as a white powder.

Provenance & Evidence