Allyl Alcohol → HCID 178458938, compound

Participants

Reaction Steps

A 250 mL round bottom flask was charged with 2,4-dichloro-5-fluoropyrimidine (10.0 g, 59.9 mmol) and allyl alcohol (8.60 mL, 126 mmol). t-BuOK (1.0 M in t-BuOH, 132 mL, 132 mmol) was then added, and a significant exotherm was observed. The resulting mixture was allowed to stir at room temperature for 5 h. The crude reaction mixture was then diluted with EtOAc (300 mL) and washed with saturated aqueous NaCl solution (200 mL×2). The organic layer was dried over MgSO4, filtered, and concentrated in a 500 mL round bottom flask. The crude mixture was diluted with ethanol (60 mL) and aqueous potassium hydroxide (2.0 M, 240 mL, 480 mmol), and the resulting biphasic mixture was heated at reflux for 18 h. After cooling to room temperature, the crude material was washed with Et2O (200 mL×2) and then acidified with 2.0 M HCl (˜215 mL) to obtain a turbid solution with a pH of 3. This mixture was then diluted with saturated aqueous NaCl solution (200 mL) and extracted with EtOAc (200 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to obtain 2-(allyloxy)-5-fluoropyrimidin-4-ol (6.47 g, 64%) as an off white solid: mp 138-141° C.; 1H NMR (300 MHz, DMSO-d6) δ 13.00 (bs, 1H), 7.84 (d, J=3.7 Hz, 1H), 5.99 (m, 1H), 5.38 (m, 1H), 5.26 (m, 1H), 4.78 (m, 2H); MS (ESI) m/z 171 (M+H)+, 169 (M−H)−.

Provenance & Evidence