1,3-Dichloro-5,5-dimethylhydantoin → 4-Amino-3-chloro-5-fluoro-6-propylpicolinaldehyde

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Reaction Steps

To a flask equipped with a stir bar and reflux condenser was added 4-amino-5-fluoro-6-propylpicolinaldehyde (0.250 g, 1.372 mmol) and 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (0.149 g, 0.755 mmol). The flask was sealed, evacuated and backfilled with N2. Acetonitrile (13.72 mL) was added, and the reaction mixture was stirred at room temperature for ˜5 min, then heated to reflux (˜2 h). The reaction mixture color changed from yellow to orange then green over the course of 2 h. The reaction mixture was cooled to room temperature, diluted with EtOAc and washed with H2O. The layers were separated, and the organic layer was washed with dilute sodium bisulfite followed by saturated NaCl. The organic layer was dried (Na2SO4), filtered and concentrated onto silica. Purification via flash chromatography (silica; EtOAc, Hex) yielded 4-amino-3-chloro-5-fluoro-6-propylpicolinaldehyde (97 mg, 32.6%) as an off-white solid: mp 89-91° C.; 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 4.81 (s, 2H), 2.81 (m, 2H), 1.76 (m, 2H), 0.99 (t, J=7.4 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −139.62; 13C NMR (101 MHz, CDCl3) δ 191.27, 152.80, 149.26, 146.64, 141.87, 139.82, 115.77, 37.04, 28.53.

Provenance & Evidence