Sodium hydride → Diethyl 2-fluoro-2-phenylmalonate

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Reaction Steps

Diethyl phenylmalonate (472 mg, 431 μL, 2 mmole) was dissolved in anhydrous tetrahydrofuran (10 mL) under nitrogen. Sodium hydride (96 mg as a 60% oil dispersion, 2.4 mmole) was added and the mixture was stirred until hydrogen evolution ceased (about 15 minutes). The solution was then cooled to -50° under nitrogen and N-fluoro-N-neopentyl-p-toluenesulfonamide (518 mg, 2 mmole, as prepared in Example 1) was added and the mixture was stirred at -50° for 15 minutes. The solution was stirred at -20° for 15 minutes, 0° for 15 minutes, and room temperature for 15 minutes before being diluted with ether (100 mL). The ether solution was washed with aqueous 1N oxalic acid (30 mL), 10% aqueous potassium bicarbonate (30 mL), and saturated aqueous sodium chloride (30 mL) solutions, and then dried over anhydrous magnesium sulfate. Filtration, removal of solvent under reduced pressure, and purification by flash column chromatography (silica, 30% methylene chloride in hexane) yielded diethyl 2-fluoro-2-phenylmalonate (410 mg, 81% yield) as a colorless oil. This material, and additional samples prepared by this procedure, were analyzed and provided the following results: IR (liquid film) γmax (cm-1) 2800 (m), 1760 (s, ester), 1420 (m), 1350 (m), 1250 (s); 1H NMR (80 MHz, CDCl3) δ1.32 (t, J=8.0 Hz, 6H, CH3), 4.33 (q, J=8 Hz, 4H, CH2), 7.50 (m, 5H); 19F NMR (94.1 MHz, CDCl3) -162.23; HRMS calcd. for C13H15O4F: 254.0954; found: 254.0947.

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