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With triethylamine; In ethyl acetate; N,N-dimethyl-formamide; |
EXAMPLE 3 N-[1-(6-ethyl-2-pyridylmethyl)piperidin-4-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide STR7 To a solution of 22 mg of <strong>[163658-33-1]6-ethyl-2-pyridine-methanol</strong> in 3 ml of ethyl acetate, 0.1 ml of triethylamine and 50 mul of methanesulfonylchloride were added at room temperature, followed by 30 minutes' stirring at the same temperature. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, followed by an hour's stirring. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The extract was combined with the organic layer, washed with saturated saline solution, dried over anhydrous magnesium sulfate and removed of the solvent by reduced pressure distillation. The residue was dissolved in 3 ml of N,N-dimethylformamide, and to the solution 32 mg of N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide as obtained in Step (2) of Example 2, 12 mg of sodium bromide and 85 mg of potassium carbonate were added, followed by 4 hours' stirring at room temperature. The reaction mixture was poured into water and extracted with diethyl ether. The extract was sequentially washed with water and saturated saline solution, dried over anhydrous magnesium sulfate and removed of the solvent by reduced pressure distillation. The residue was purified by preparative thin layer chromatography [Kieselgel 60F254, Art 5744 (Merck), chloroform/methanol=12/1] to give 14.5 mg of the title compound as a white solid. FAB-MS (m/e, (C26 H35 N3 O2 +H)+) 422 1 H-NMR(CDCl3) delta: 1.15-1.34 (1H, m), 1.29 (3H, t, J=7.5 Hz), 1.38-1.92 (11H, m), 2.17-2.30 (2H, m), 5 2.70-2.89 (2H, m), 2.81 (2H, q, J=7.5 Hz), 2.97-3.22 (2H, m), 3.63 (2H, s), 3.67-3.81 (1H, m), 6.35 (1H, brd, J=7.7 Hz), 7.04 (1H, d, J=7.3 Hz), 7.21 (1H, d, J=7.9 Hz), 7.24-7.40 (3H, m), 7.53-7.65 (3H, m) |