Phosphorus oxychloride → 4-Chloro-3-nitroquinoline

Participants

Reaction Steps

Phosphorous oxychloride (84.3 g, 0.55 mol) was added to a stirred suspension of 3-nitroquinolin-4-ol (95.0 g, 0.50 mol) in DMF (500 mL), and an exotherm was observed. After the addition was complete, the solution was heated on a steam bath for 15 minutes. The solution was poured over ice to precipitate 4-chloro-3-nitroquinoline. The 4-chloro-3-nitroquinoline was isolated by filtration, washed with water, and pressed dry. The 4-chloro-3-nitroquinoline was dissolved in dichloromethane (1 L) and the solution was dried over magnesium sulfate and filtered. 2-(2-Aminoethoxy)ethanol (60.7 g, 0.6 mol) and triethylamine (104 mL, 0.75 mol) were added to the filtrate. The resulting solution was heated at reflux for 30 minutes. The mixture was concentrated under reduced pressure. The residue was dissolved in dilute aqueous hydrochloric acid and filtered. Ammonium hydroxide was added to the filtrate and a yellow solid formed. The solid was isolated by filtration, washed with water, and dried to provide 104.5 g of 2-{2-[(3-nitroquinolin-4-yl)aniino]ethoxy}ethanol as a yellow solid.

Provenance & Evidence