Trifluoroacetic acid → (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzoyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

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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 (300 mg, 0.65 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 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), triethylamine (2 ml) and 4-trifluoromethoxybenzoyl chloride (0.15 ml, 0.98 mmol). The reaction mixture was stirred at room temperature for 1 hour, then poured into water, and extracted with methylene chloride. 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/ethyl acetate=10/1) and crystallized from methylene chloride-diisopropyl ether to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzoyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (263 mg, yield 74%) as a white powder.

Provenance & Evidence