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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence