Potassium Carbonate → HCID 22993884, compound

Participants

Reaction Steps

2-Fluoro-5-nitroacetophenone (3.6 g, 20 mmol, described by Cooper, et. al. J. Med. Chem. 33:1246-1252 (1990)) and 5-chloro-3-pyridinol (3.2 g, 25 mmol) were dissolved in acetone (20 mL). After addition of solid K2CO3 (3.5 g, 26 mmol), the reaction mixture was heated to reflux for 4 hr. The reaction mixture was cooled and acetone was removed under reduced pressure. The residue was suspended in deionized water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic portions were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a brown oil which was partially purified by column chromatography (silica gel, 4:1 hexanes:ethyl acetate) to provide 4 g of 2-(5-chloro-3-pyridyloxy)-5-nitro-1-phenylethanone. This material was dissolved in ethanol (40 mL) and acetic acid (5.3 mL, 93 mmol) to which iron powder (300 mesh, 2.6 g, 46.5 mmol) was added. The reaction mixture was heated to reflux for two days. After removal of excess iron (with a magnetic stir-bar retriever), the reaction mixture was poured into 300 mL of deionized water and extracted with ethyl acetate (3×100 mL). The combined organic portions were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a brown oil which was purified by column chromatography (silica gel, 4:1 hexanes:ethyl acetate). The product 5′-amino-2′-(5-chloro-3-pyridyloxy)-1-phenylethanone was obtained as a yellow oil (1.03g).

Provenance & Evidence