反应详情

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 (5 ml), triethylamine (2 ml) and ethyl chloroformate (0.11 ml, 1.31 mmol) followed by stirring at room temperature for 1 hour. The reaction mixture was 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/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford ethyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (182 mg, yield 65%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. stirringby stirring at room temperature for 1 hour
3. extractionextracted with methylene chloride
4. washThe organic phase was washed with a saturated saline solution
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationThe resulting filtrate was concentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
9. customcrystallized from methylene chloride-isopropyl ether