反应详情

The tert-butyl 4-(1-cyano-2-oxoethyl)piperidine-1-carboxylate (757 mg, 3.0 mmol) obtained in Step 4 of Example 1 was dissolved in methanol (6 mL) and water (2 mL), diethyl aminomalonate hydrochloride (952 mg, 4.5 mmol) and sodium acetate (492 mg, 6.0 mmol) were added, followed by stirring at room temperature for 18 hours. The reaction liquid was concentrated under a reduced pressure and dissolved in chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue (1.53 g) was dissolved in ethanol (6 mL), and then sodium ethoxide (510 mg, 7.5 mmol) was added, followed by heating under reflux for 3 hours. The reaction liquid was concentrated under a reduced pressure, and the obtained residue was dissolved in ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue was purified by using silica gel chromatography (chloroform:methanol=100:1→50:1) to give tert-butyl 4-[4-amino-5-(ethoxycarbonyl)-1H-pyrrol-3-yl]piperidine-1-carboxylate (466 mg, 46.0%) as a pale yellow amorphous.

1. customThe reaction liquid
2. concentrationwas concentrated under a reduced pressure
3. dissolutiondissolved in chloroform
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under a reduced pressure
7. dissolutionThe obtained residue (1.53 g) was dissolved in ethanol (6 mL)
8. temperatureby heating
9. temperatureunder reflux for 3 hours
10. customThe reaction liquid
11. concentrationwas concentrated under a reduced pressure
12. dissolutionthe obtained residue was dissolved in ethyl acetate
13. washThe organic layer was washed with saturated brine
14. dry with materialdried over anhydrous sodium sulfate
15. concentrationconcentrated under a reduced pressure
16. customThe obtained residue was purified