Piperidine → 1-(2-(4-Nitrophenoxy)ethyl)piperidine

Participants

Reaction Steps

A solution of 1-(2-chloroethoxy)-4-nitrobenzene (2.01 g, 0.01 mol), piperidine (2.55 g, 0.03 mol), and toluene (10 mL) was refluxed overnight. The reaction mixture was filtered and the filtrate evaporated to give 2.97 g of 1-[2-(1-piperidinyl)ethoxy]-4-nitrobenzene as an orange oil, MS M+ (m/e) 251.18. This material (1.25 g, 0.004 mol) was hydrogenated in ethanol (25 mL) in the presence of 10% Pd-C catalyst at 40 psig and 25° C. overnight. Filtration and evaporation of the reaction mixture gave 0.95 g of 4-[2-(1-piperidinyl)ethoxy]aniline as a light brown oil, MS M+ (m/e) 221.24. A solution of this oil (0.220 g, 1.0 mmol), 3-methyl-5,8-dimethoxy-2-tetralone (6, 0.206, 0.94 mmol), and 1,2-dichloroethane (3.5 mL) was treated with sodium triacetoxyborohydride (0.300 g, 1.4 mmol) and acetic acid (0.060 g, 1.0 mmol) and the resulting mixture was stirred overnight at 25° C. The reaction was treated with 3N sodium hydroxide solution with vigorous stirring. The organic layer was separated, washed with saturated sodium chloride solution, dried over potassium carbonate, filtered and evaporated to a red oil. This material was purified by C-18 reverse phase high pressure liquid chromatography affording compound 60 as a pink solid. 1H NMR (300 MHz, CDCl3): δ 7.10–7.22 (m, 2H), 6.52–6.82 (m, 4H), 4.25–4.33 (m, 2H), 3.60–3.80 (m, 3H), 3.75 (s, 3H), 3.71 (s, 3H), 3.48–3.38 (m, 2H), 2.80–3.05 (m, 4H), 1.80–2.10 (m, 4H), 1.10–1.50 (m, 3H), 1.00 (d, 3H). MS M+ (m/e) 425.38.

Provenance & Evidence