Reaction Steps
A mixture of 1′-(piperidin-4-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.37 g, 0.99 mmol), acetaldehyde (0.08 mL, 1.4 mmol) and sodium triacetoxyborohydride (0.32 g, 1.51 mmol) in 1,2-dichloroethane (4 mL) was stirred at ambient temperature for 17.5 h. The orange reaction mixture was diluted with saturated aqueous sodium bicarbonate (30 mL) and was extracted with dichloromethane (3×25 mL). The organic solution was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash column chromatography with dichloromethane/methanol (19:1) afforded 1′-[(1-ethylpiperidin-4-yl)methyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.32 g, 80%) as a yellow foam: 1H NMR (300 MHz, CDCl3) δ7.29 (ddd, J=7.8, 7.8, 1.4 Hz, 1H), 7.15 (dd, J=7.5, 0.9 Hz, 1H), 7.04 (ddd, J=7.5, 7.5, 0.8 Hz, 1H), 6.90 (d, J=8.1 Hz, 1H), 6.45 (s, 1H), 6.41 (s, 1H), 4.90 (d, J=9.0 Hz, 1H), 4.66 (d, J=9.0 Hz, 1H), 4.53 (t, J=8.6 Hz, 2H), 3.73 (dd, J=14.0, 7.4 Hz, 1H), 3.60 (dd, J=14.0, 7.1 Hz, 1H), 3.10-2.95 (m, 4H), 2.52 (q, J=7.1 Hz, 2H), 2.14-1.87 (m, 3H), 1.83-1.72 (m, 2H), 1.67-1.52 (m, 2H), 1.15 (t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ178.2, 161.9, 161.5, 143.0, 132.9, 128.9, 124.1, 123.4, 120.3, 120.0, 118.9, 108.8, 93.4, 80.9, 72.5, 57.8, 52.6, 45.8, 34.5, 29.6, 29.5, 29.2, 11.7; MS (ES+) m/z 405.2 (M+1).
