Tetrahydrofuran → HCID 67784806, compound

Participants

Reaction Conditions

Reaction Steps

n-Butyl lithium (5.27 ml, 7.80 mM) in THF was added dropwise to a solution of 4-[2-piperidinoethoxy]phenyl bromide (1.45 g, 7.80 mmol) in THF (5 ml) at -78° C. After stirring for 30 minutes at -78° C., 2-(p-chlorobenzyl)-6-methoxy-3(2H)- benzofuranone (1.50 g, 5.20 mmol) in THF was added dropwise to the mixture at -78° C. The reaction mixture was stirred at -78° C. for 1 hour. It was warmed to room temperature. After stirring for 18 hours, it was quenched with saturated ammonium chloride and THF was evaporated off. The residue was dissolved in ethyl acetate (30 ml), washed with sodium chloride (2×20 ml), dried (anhydrous magnesium sulphate) and the solvent evaporated off to yield an oil which was purified by flash chromatography (eluent, dichloromethane:hexane:triethylamine=1:1:0.2), yielding a light brown oil of the tertiary alcohol, 2-(p-chlorobenzyl)-3-[p-(2-piperidinoethoxy)phenyl]- 6-methoxybenzofuranol (Rf =0.23) which gave a characteristic reddish stain with ammonium molybdate-ceric sulphate in 2M sulphuric acid spray. A solution of methanol (0.40 ml) saturated with dry hydrogen chloride gas was added to the tertiary alcohol dissolved in sodium-dried ether (40 ml). The reaction mixture was stirred at room temperature for 1/2 hour. A white precipitate was formed which was filtered and recrystallised from ethanol to give the hydrochloride salt of the title compound as a white crystalline solid. Yield (74 %); m.p. 133°-136° C.; 1H-NMR (CDCl3)δ 1:58-3.03 (bm, 10H, N(CH2CH2)2CH2), 3.42 (t, 2H, J 6.0 Hz, OCH2CH2N), 3.85 (s, 3H, OCH3), 4.10 (s, 2H, CH2 at C-2), 4.44 (t, 2H, J 6.0 Hz, OCH2CH2N), 6.81-7.44 (m, 11H, ArH); m/z (%) 477 (M+ -HCl, 8), 475 (M+ -HCl, 3), 364 (13), 98 (100). (Found: C, 64.89, H, 6.20, N, 2.49, Cl, 13.38. C29H30O3ClN.HCl.3/2H2O required C, 64.56, H, 6.35, N, 2.60, Cl, 13.14).

Provenance & Evidence