Cyclobutanone → N-[2-(1-Hydroxycyclobutyl)phenyl]formamide

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Reaction Steps

Sodium hydride (65% dispersion in mineral oil, 71 mg, 1.775 mmol) was suspended in tetrahydrofuran (6 mL), and to this stirred slurry was added dropwise a solution of N-(2-iodophenyl)formamide (250 mg, 1.012 mmol) in tetrahydrofuran (4 mL). The mixture was stirred at room temperature for 20 minutes, then chilled to −78° C. To the cold suspension was added dropwise 2.5 M n-butyllithium in hexanes (0.506 ml, 1.265 mmol). The mixture was stirred at −78° C. for 30 minutes, then cyclobutanone (0.083 ml, 1.113 mmol) was added dropwise. The mixture was stirred at −78° C. for 2 hours and quenched with saturated NH4Cl (20 mL) solution and warmed to room temperature. The mixture was extracted with ethyl acetate (3×30 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The product was purified by flash chromatography (Analogix, 20 to 50% ethyl acetate-hexanes over 25 min, 4 g silica cartridge, 18 mL/min) to give the title compound as a 2:1 ratio of two rotational isomers.

Provenance & Evidence