Diethyl Malonate → Diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate

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Reaction Steps

To a stirred suspension of sodium hydride (920 mg, 23 mmol, 60% in mineral oil) in dry dioxane (33 mL), was added diethyl malonate (3.5 mL, 23 mmol) dropwise over min. After the addition was complete, (((1-bromo-3-chloropropan-2-yl)oxy)methyl)benzene (157) (6.1 g, 23 mmol) was added over 20 minutes. The mixture was then heated at reflux for 24 hours. After cooling to room temperature, sodium hydride (920 mg, 23 mmol) in dioxane (2 mL) was added to the mixture and heating at reflux for another 48 hours. The solvent was partially removed under reduced pressure and the mixture was treated with water (50 mL). The mixture was extracted with ethyl acetate (3×30 mL), dried with magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography using hexanes/ethyl acetate as eluent (25%) to yield diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate (158). 1H NMR (400 MHz, CD2Cl2) δ 7.39-7.30 (m, 5H), 4.4 (s, 2H), 4.23-4.13 (m, 5H), 2.83-2.78 (m, 2H), 2.55-2.49 (m, 2H), 1.32-1.25 (m, 6H). MS m/z 307.2 (M+1)+.

Provenance & Evidence