Diisopropyl Ether → 7-[(4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of 7-amino-quinoline-3-carboxylic acid ethyl ester (11 g, 51 mmol, 1 equiv), dichloroethane (220 mL, 20 volumes), and diisopropylethylamine (13.15 g, 101.7 mmol, 2 equiv) was slowly added a solution of 4′-trifluoromethyl-biphenyl -2-carbonyl chloride (17.38 g, 61 mmol, 1.2 equiv) dissolved in dichloroethane (30 mL, 2.7 volumes). The reaction was heated at 84° C. overnight and then cooled to room temperature. The reaction mixture was washed with 1 N hydrochloric acid (2×150 mL) and the aqueous layer was back extracted with dichloroethane (1×150 mL). The combined organic layers were washed with 1 N sodium hydroxide (2×150 mL), water (150 mL), and saturated sodium chloride (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo to give a red-brown oil. The oil was dissolved in hot toluene (32 mL) and isopropyl ether (16 mL) and the resulting solution was allowed to cool with stirring to give a beige slurry. The solids were collected by filtration to give 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester (13.8 g, 58.4%).

Provenance & Evidence