Water → 3-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 6-phenoxy-2H-pyridazin-3-one (0.78 g, 4.18 mmol) in tetrahydrofuran (21 mL, 0.2M) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (0.2 g, 5.0 mmol). The reaction was stirred at 0° C. for 5 min and then at 25° C. for 35 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 1.08 g, 4.59 mmol). The reaction was then warmed to 50° C. where it stirred overnight. After this time, the reaction was cooled to 25° C., poured into water (100 mL), and extracted into methylene chloride (3×100 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, rinsed with methylene chloride and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 80 g, 20-40% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid methyl ester (1.03 g, 72%) as a light yellow oil. 1H-NMR (300 MHz, DMSO-d6) δ ppm 0.98 (d, 2H), 1.32-1.71 (m, 7H), 1.71-1.84 (m, 1H), 1.84-2.05 (m, 1H), 3.59 (s, 3H), 5.19 (dd, J=10.9, 3.9 Hz, 1H), 7.10-7.18 (m, 3H), 7.22 (t, J=7.5 Hz, 1H), 7.42 (t, J=7.5 Hz, 2H), 7.48 (d, J=9.7 Hz, 1H).

Provenance & Evidence