N-Ethylaniline → Laquinimod

Participants

Reaction Conditions

Reaction Steps

The mixture of 1,2-dihydro-4-hydroxy-5-chloro- 1 -methyl-2-oxo-quinoline-3-carboxylic acid (15 gm) and methylene chloride (105 ml) was cooled to 5-10° C. under nitrogen atmosphere. Diisopropylethyl amine (26.7 gm) was added to the resulting mass for 5 minutes at 5-10° C. to form a clear solution. The solution was followed by the addition of N-ethyl aniline (7.8 gm) in one portion at 5-10° C. and then thionyl chloride (9.1 gm) was added at 5-10° C. The resulting mixture was stirred for 7 hours followed by evaporation of methylene chloride under vacuum. The resulting residue was dissolved in ethyl acetate (200 ml) followed by washings with 5% sodium hydroxide solution (65 ml) at 25-30° C. The resulting aqueous layer was cooled to 10-15° C. followed by adjusting pH of the mass to 1 by using 18% aqueous hydrochloric acid solution (25 ml). The resulting mass was stirred for 1 hour at 10-15° C. The separated white colored solid was filtered and dried at 55-60° C. to yield 19.3 gm of laquinimod (HPLC Purity: 98.41%).

Provenance & Evidence