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

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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 3 hours. The reaction mixture was concentrated under reduced pressure and then added methylene chloride (2 ml) and triethylamine (2 ml). After stirring at room temperature for 5 minutes, the solution was concentrated under reduced pressure, and the residue was dissolved in DMF (15 ml). To the solution, a mixture of 4-chlorobenzyl alcohol (186 mg, 1.31 mmol), 1,1′-carbonyldiimidazole (212 mg, 1.31 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, extracted from 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. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford 4-chlorobenzyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (313 mg, yield 91%) as a light yellow powder.

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