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

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]+.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customThe residue was partitioned between dichloromethane (2×50 ml) and 10% aqueous sodium carbonate (20 ml)
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe 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)

ORD record

ord-67ce5fc3b1654f22bba6e53fde9324e7

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456164B2