Diethyl 2-Fluorobenzylphosphonate → (E)-2-Bromo-5-fluoro-4-(2-fluorostyryl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromo-5-fluoroisonicotinaldehyde (2 g, 9.80 mmol) and diethyl 2-fluorobenzylphosphonate (2.66 g, 10.78 mmol) in tetrahydrofuran (80 mL) at 0° C., was added potassium tert-butoxide(1M in tetrahydrofuran, 12.75 mL, 12.75 mmol) dropwise over a couple of minutes. When addition was complete, the reaction was allowed to stir at 0° C. for 45 min and quenched by addition of saturated ammonium chloride. The reaction was diluted with ether, washed with water (4×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture. The material was triturated with hexanes (2×) to give a fine white powder. 1H NMR (CDCl3) δ: 8.26 (d, J=1.5 Hz, 1H), 7.69 (d, J=5.5 Hz, 1H), 7.64 (td, J=7.6, 1.5 Hz, 1H), 7.54 (d, J=16.8 Hz, 1H), 7.30-7.41 (m, 1H), 7.17-7.26 (m, 2H), 7.11-7.17 (m, 1H). 13C NMR (CDCl3) δ: 161.0, 156.7, 138.8, 136.6, 135.5, 131.0, 129.3, 127.9, 124.6, 123.7, 119.4, 116.3. 19F NMR (CDCl3) δ: −116.72 (br. s., 1F), −136.08 (br. s., 1F).

Provenance & Evidence