Ammonium Hydroxide → 4-Methoxy-7-cyanoindole

Participants

Reaction Conditions

Reaction Steps

To an oven dried 500 ml round bottom flask at rt. was charged with 4-methoxy-7-bromo-indole intermediate 5 (12.8 g, 56.6 mmol) and dry DMF (120 ml), followed by CuCN (25.3 g, 283 mmol). The reaction mixture was refluxed at 165° C. for 16 hr. After cooling to rt., the mixture was slowly added ammonium hydroxide (100 ml), stirred for 10 min, concentrated in vacuo to ˜50 ml and diluted with CHCl3 (250 ml). The organic mixture was washed with H2O (250 ml), and the aqueous layer back extracted with CHCl3 (2×200 ml). The combined organic extracts were filtered through a filter paper to remove some solids, and washed again with H2O (100 ml) and brine (100 ml), and then dried (MgSO4). After evaporation in vacuo, the residue was purified by flash column chromatography (10% EtOAc/Hexane (250 ml), then 25% EtOAc/Hexanes (1250 ml)) to afford 4-methoxy-7-cyanoindole intermediate 35 (8.0 g, 82%) as yellow solids. 1H NMR: (CDCl3) δ 8.73 (b s, 1H), 7.50 (d, J=8.3 Hz), 7.22 (app t, J=2.8 Hz, 1H), 6.73 (dd, J=2.3, 3.2 Hz, 1H), 6.58 (d, J=8.3 Hz, 1H), 4.01 (s, 3H); LC/MS: (ES+) m/z (M+H)+=173, HPLC (YMC C18 S7 3×50 mm, Flow Rate 4 ml/min, Gradient Time 3 min) Rt=1.700.

Provenance & Evidence