Triethylamine → Tasquinimod

Participants

Reaction Steps

To an ice-cold solution of 1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxylic acid (8 g, 0.032 mol), triethylamine (15.5 ml, 0.11 mol) and 4-trifluoromethyl-N-methylaniline (6.1 g, 0.035 mol) in 150 ml of dichloromethane, a solution of thionyl chloride (3.0 ml, 0.042 mol) in 10 ml of dichloromethane was added dropwise during 0.5 hours. The stirring was continued at 4° C. for 4 hours. The solution was diluted with 10 ml of dichloromethane, washed with cold 1 M sulfuric acid and then extracted with 1 M sodium hydroxide. The pH of the aqueous phase was adjusted to 8-8.5, and the aqueous solution was clarified by filtration and then acidified with hydrochloric acid to pH 4. On standing a crystalline precipitate was formed which was filtered off, washed with water and dried to give the title compound (8.5 g), yield 65%.

Provenance & Evidence