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 (118 mg, 0.26 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added, and the mixture was stirred at room temperature for 3 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 DMF (15 ml) and the solution was added a solution of 3,4-dichlorobenzyl alcohol (136 mg, 0.77 mmol) and 1,1′-carbonyldiimidazole (125 mg, 0.77 mmol) in DMF (5 ml) stirred at room temperature for 3 hours followed by stirring at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. 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 3,4-dichlorobenzyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (101 mg, yield 70%) as a light yellow 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 DMF (15 ml)
6. stirringstirred at room temperature for 3 hours
7. stirringby stirring at room temperature overnight
8. extractionextracted with ethyl acetate
9. washThe organic phase was washed with a saturated saline solution
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationThe resulting filtrate was concentrated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
14. customcrystallized from methylene chloride-isopropyl ether