Potassium Iodide → 1-(2-Methoxyethyl)-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile

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Reaction Steps

A mixture of 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile (68 mg, 0.22 mmol), 2-bromoethylmethylether (21 μl, 0.22 mmol), solid sodium bicarbonate (84 mg, 1.0 mmol) and potassium iodide (5 mg, catalytic) was heated at 50° C. in acetonitrile (1 ml) for 18 hours. The reaction mixture was concentrated in vacuo. The residue was partitioned between dichloromethane (2×50 ml) and 10% aqueous sodium carbonate (20 ml). The organic layers were combined, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 95:5:0.5 by volume) to provide the title compound (46 mg, 61%). 1H NMR (400 MHz, CD3OD) 61.83-1.87 (m, 4H), 2.01-2.10 (m, 6H), 2.45-2.52 (m, 2H), 2.65-2.69 (m, 6H), 2.75 (t, 2H), 3.09 (d, 2H), 3.35 (s, 3H), 3.56 (t, 2H), 4.04 (t, 2H), 6.96 (d, 2H), 7.42 (d, 2H). HRMS ESI+ m/z 372.2639 [MH]+.

Provenance & Evidence