tert-Butanol → 1,4,6-Trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

온도

90 °C

To a solution of 2.36 g (23.8 mmol) of (Z)-4-aminopent-3-en-2-one in 8 mL of toluene was added 5.88 g (40.5 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 4.65 g (48.4 mmol) of t-BuONa and 4 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 20 mL of sat aq NH4Cl. The mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (25 2.6 cm). Elution with 10:1 hexanes/ethyl acetate gave the product as a yellow oil: yield 1.60 g (42%); silica gel TLC Rf 0.15 (4:1 hexanes/ethyl acetate); 1H NMR (CDCl3) δ 2.05 (s, 3H), 2.32 (s, 3H), 2.76 (t, 2H, J=8.4 Hz), 2.86 (s, 3H), 3.34 (t, 2H, J=8.4 Hz) and 6.10 (s, 1H); 13C NMR (CDCl3) δ 17.8, 24.0, 24.3, 33.1, 52.4, 113.1, 118.1, 141.2, 154.5 and 163.7; mass spectrum, m/z 162.1 (M+) (theoretical 162.1).

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 20 mL of sat aq NH4Cl
6. extractionThe mixture was extracted with EtOAc
7. washThe combined organic layer was washed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated under diminished pressure
10. customThe residue was purified by flash chromatography on a silica gel column (25 2.6 cm)
11. washElution with 10:1 hexanes/ethyl acetate

ORD 기록

ord-6ce6ab76ebb241c7a443889f91f5ec57

출처 데이터셋

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09440967B2