Hydroquinone → HCID 45381861, compound

Participants

Reaction Conditions

Reaction Steps

Sodium dispersion in paraffin (30%; 162 mg, 2.11 mmol; Aldrich) was combined with 9-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole (290 mg, 0.996 mmol; Example 174A) in a 20 mL vial with stir bar and septum cap. Dimethyl sulfoxide (4.0 mL) was added, and the vial was evacuated and purged with nitrogen (10 cycles). The mixture was stirred at room temperature for 30 minutes, and a solution of 4-chlorostyrene (213 mg, 1.54 mmol; Aldrich) and hydroquinone (53 mg, 0.48 mmol; Aldrich) in dimethyl sulfoxide (2 mL) was added. The vial was evacuated and purged with nitrogen (5 cycles) and the mixture was stirred with heating at 105° C. for 110 hours. The mixture was cooled to room temperature, diluted with water (100 mL) and 25% NaOH (2 mL) and extracted with chloroform (3×50 mL). The combined organic phase was concentrated and the residue was purified by flash chromatography (silica, eluted with CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1). The product-containing fractions were combined and concentrated under vacuum to provide a residue (140 mg), which was further purified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes] to provide the title compound: 1H NMR (300 MHz, CDCl3) δ 1.60-1.74 (m, 2H), 1.81-1.97 (m, 2H), 2.80-2.88 (m, 1H), 2.97 (t, J=6.8 Hz, 2H), 3.00-3.08 (m, 2H), 3.25 (ddd, J=14.1, 9.0, 5.4 Hz, 2H), 4.20-4.31 (m, 2H), 4.24 (s, 2H), 6.88-6.94 (m, 2H), 7.09 (d, J=7.8 Hz, 1H), 7.21 (d, J=7.1 Hz, 1H), 7.20-7.25 (m, 2H), 7.50 ppm (d, J=1.7 Hz, 1H); MS (DCI) m/z 429/431/433 (M+H)+.

Provenance & Evidence