N-Ethylaniline → Laquinimod

Participants

Reaction Conditions

Reaction Steps

1,2-Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid (2 gm) and N-ethyl aniline (1 gm) were taken in toluene (50 ml) and stirred for 30 minutes at 25-30° C. under nitrogen atmosphere. The resulting mass was followed by the addition of dichlorotriphenyl phosphorane (10.5 gm) at 25-30° C., followed by heating to reflux (110-115° C.) and then maintained for 3 hours at reflux. Toluene was distilled out from the reaction mass under vacuum at below 60° C. The resulting residue was dissolved in ethyl acetate (100 ml) at 25-30° C. followed by the addition of water (100 ml) at 25-30° C. and then pH of the resulting mass was adjusted to 10-12 with 10% sodium hydroxide solution at 25-30° C. The resulting mass was stirred for 30 minutes at 20-25° C. followed by separation of the layers. The resulting aqueous layer was cooled to 15-20° C. and pH was adjusted to 2 by using concentrated hydrochloric acid. The resulting mass was stirred for 30 minutes at 15-20° C. The separated solid was filtered, washed with water and then dried to yield 2 gm of laquinimod (HPLC purity: 98.4%).

Provenance & Evidence