反应详情

温度

90 °C

To a solution containing 1.20 g (12.1 mmol) of 4-amino-3-penten-2-one in 8 mL of toluene was added 3.00 g (20.7 mmol) of 2,2-Dimethoxy-1-methylpyrrolidine. The reaction mixture was heated at reflux and stirred for 2 h, cooled to 90° C., and then treated with 2.38 g (24.8 mmol) of t-BuONa and 2 mL of t-BuOH. The reaction mixture was stirred at 90° C. for another 16 h. The cooled reaction mixture was quenched by the addition of 10 mL of sat aq. NH4Cl. The mixture was extracted with three 30-mL portions of EtOAc. The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under diminished pressure. The residue was purified via flash chromatography on a silica gel column (42×2.5 cm). Step gradient elution with 1:4→1:1 ethyl acetate-hexanes as eluent gave 1,4,6-trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine as a brown oil: yield 0.62 g (32%); silica gel TLC Rf 0.15 (1:4 ethyl acetate-hexanes); 1H NMR (CDCl3) 1.91 (s, 3H), 2.20 (s, 3H), 2.65 (t, 2H, J=8.4 Hz), 2.76 (s, 3H), 3.23 (t, 2H, J=8.4 Hz), 5.98 (s, 1H).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux
3. stirringThe reaction mixture was stirred at 90° C. for another 16 h
4. customThe cooled reaction mixture
5. customwas quenched by the addition of 10 mL of sat aq. NH4Cl
6. extractionThe mixture was extracted with three 30-mL portions of EtOAc
7. washThe combined organic layer was washed with brine
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated under diminished pressure
11. customThe residue was purified via flash chromatography on a silica gel column (42×2.5 cm)
12. washStep gradient elution with 1:4→1:1 ethyl acetate-hexanes as eluent