A mixture of tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylate prepared in Example 393 (1.17 g, 3.32 mmol), trifluoroacetic acid (5 ml) and methylene chloride (10 ml) was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride (10 ml). To the resulting solution, triethylamine (5 ml, 35.87 mmol) was added followed by stirring at room temperature for 10 minutes. The solution was concentrated under reduced pressure, the residue was dissolved in DMF (15 ml). To the mixture, potassium carbonate (920 mg, 6.64 mmol) and a solution of 4-(4-trifluoromethylphenyl)-piperidine-1-carbonylchloride (1.07 g, 3.65 mmol) in DMF (10 ml) was added slowly with cooling on ice-bath followed by stirring at room temperature overnight. To the reaction mixture, water was added followed by extraction with ethyl acetate. The extract was washed with water three times and a saturated saline solution, dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=30/1) to afford (S)-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]-[4-(4-trifluoromethylphenyl)piperidin-1-yl]methanone (575 mg, yield 33%) as a white powder.
