5-Nitroindole → tert-Butyl 4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of sodium (2.51 g, 105 mmol, 7 eq) in absolute methanol (50 mL) was added 5-nitroindole (2.43 g, 15.0 mmol) and N-t-butoxycarbonyl4-piperidone (8.96 g, 45.0 mmol, 3.0 eq). The resulting reaction solution was heated at reflux (65° C.) under nitrogen for 24 hours. The resulting reaction solution was evaporated under reduced pressure, and the residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL). The organic layer was removed, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure. Column chromatography of the extraction residue using silica gel (approximately 100 g) and elution with ethyl acetate in hexanes [1:2 to 1:1 gradient] afforded the title compound (72%) as yellow solid: mp, decomposes 230° C.; 1H NMR (CDCl3) δ 9.24 (br s, 1H), 8.78 (d, J=1.3 Hz, 1H), 8.09 (dd, J=1.4 and 9.4 Hz, 1H), 7.40 (d, J=9.3 Hz, 1H), 7.30 (d, J=1.8 Hz, 1H), 6.17-6.15 (m, 1H), 4.16-4.13 (m, 2H), 3.68 (t, J=5.8 Hz, 2H), 2.58-2.48 (m, 2H), 1.50 (s, 9H); Anal. calcd for C15H21N3O4.0.1 H2O: C, 62.63; H, 6.19; N, 12.17. Found: C, 62.71; H, 6.09; N, 11.81.

Provenance & Evidence