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 (4.22 g, 9.60 mmol) was dissolved in methylene chloride (10 ml). To the solution, trifluoroacetic acid (30 ml) was added followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (10 ml) and triethylamine (10 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure. The residue was dissolved in dichloroethane. To the solution, 4-trifluoromethoxybenzaldehyde (1.64 ml, 11.5 mmol) and sodium triacetoxyborohydride (3.05 g, 14.4 mmol) were added with cooling on ice-bath followed by stirring at room temperature overnight. To the reaction mixture, a saturated sodium hydrogencarbonate solution and methylene chloride were added, and the solution was stirred and extracted with methylene chloride. The organic phase was 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 then crystallized from methylene chloride-ethyl acetate to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (3.23 g, yield 63%) as a light yellow powder.
