To a solution of (4-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-yl)methylamine (100 mg, 0.301 mmol) in toluene (2 ml) was added ethyl-4-bromobutyrate (43 μl, 0.301 mmol), N,N-diisopropylethylamine (157 μl, 0.904 mmol) and potassium iodide (5 mg, 0.030 mmol). Reaction mixture heated at 80° C. for 48 hours, then increased to reflux. Potassium carbonate (83 mg, 0.602 mmol) was added and reaction left at reflux for a further 24 hours until reaction complete. Reaction mixture was partitioned between ethyl acetate (20 ml) and saturated NaHCO3 (10 ml). Organic washings were dried over Na2SO4 and concentrated in vacuo to give a brown oil (101 mg crude, 84%). The compound was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:ammonia, 100:0:0 to 98:2:0.2, to give the title compound as an oil (7 mg, 6%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 7.90 (d, 2H), 4.22-4.36 (m, 1H), 4.80-4.90 (m, 2H), 3.52-3.67 (m, 2H), 3.40 (s, 2H), 2.72-3.88 (several multiplets, 3H), 2.50 (t, 2H), 2.34-2.44 (m, 2H), 2.21-2.30 (t, 2H), 1.60-2.10 (several multiplets, 10H), 1.08 (d, 6H).
