反应详情

Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]-piperazine-1-carboxylate prepared in Example 131 (88 mg, 0.19 mmol) was dissolved in trifluoroacetic acid (5 ml), and the solution was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (2 ml) and triethylamine (2 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure. The residue was dissolved in dichloroethane and added 4-trifluoromethylbenzaldehyde (40 μl, 0.29 mmol) and sodium triacetoxyborohydride (82 mg, 0.38 mmol) with cooling on ice-bath followed by stirring at room temperature overnight. To the solution, a saturated sodium hydrogencarbonate solution and methylene chloride were added. The mixture was extracted with methylene chloride, and the organic phase was dried over magnesium sulfate and 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-ethyl acetate to afford 2-methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (53 mg, yield 53%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionadded methylene chloride (2 ml) and triethylamine (2 ml)
3. stirringThe solution was stirred at room temperature for 5 minutes
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in dichloroethane
6. temperaturewith cooling on ice-bath
7. stirringby stirring at room temperature overnight
8. extractionThe mixture was extracted with methylene chloride
9. dry with materialthe organic phase was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationThe resulting filtrate was concentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
13. customcrystallized from methylene chloride-ethyl acetate