反应详情

Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazol-2,4′-piperidin]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate prepared in Example 653 (300 mg, 0.67 mmol) was dissolved in methylene chloride (5 ml) To the solution, trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure. To the residue, methylene chloride (1 ml) and triethylamine (1 ml) were added. The reaction mixture was stirred at room temperature for 5 minutes and concentrated under reduced pressure, and the residue was dissolved in DMF (15 ml). To the solution, a mixture of 4-trifluoromethylbenzyl alcohol (293 mg, 1.67 mmol), 1,1′-carbonyldiimidazole (270 mg, 1.67 mmol) and 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 and extracted with ethyl acetate, and the organic phase was washed with a saturated saline solution and dried over magnesium sulfate. After filtration, 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-trifluromethylbenzyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidin]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate (324 mg, yield 88%) as a light pink powder.

1. additionwas added
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additionTo the residue, methylene chloride (1 ml) and triethylamine (1 ml) were added
4. stirringThe reaction mixture was stirred at room temperature for 5 minutes
5. concentrationconcentrated under reduced pressure
6. dissolutionthe residue was dissolved in DMF (15 ml)
7. stirringstirred at room temperature for 3 hours
8. additionwas added
9. stirringby stirring at room temperature overnight
10. extractionextracted with ethyl acetate
11. washthe organic phase was washed with a saturated saline solution
12. dry with materialdried over magnesium sulfate
13. filtrationAfter filtration
14. concentrationthe resulting filtrate was concentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
16. customcrystallized from methylene chloride-isopropyl ether