Dimethylformamide → 2-[2-(2,4-Dichloro-phenyl)-acetylamino]-nicotinic acid methyl ester

Participants

Reaction Steps

Oxalyl chloride (0.14 ml) was added dropwise to a solution of (2,4-dichloro-phenyl)-acetic acid (270 mg) in dichloromethane (10 ml) at ambient temperature. A drop of N,N-dimethylformamide (“DMF”) was added to initiate the reaction. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated to give a colourless oil which was dissolved in dichloromethane (3 ml). The mixture was added dropwise to a cooled (−5° C.) slurry of 2-amino-nicotinic acid methyl ester (200 mg) (Example 1.1), 4-dimethylaminopyridine (“DMAP”) (32 mg) and pyridine (0.19 ml) in dichloromethane (5 ml). The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between dichloromethane and aqueous hydrochloric acid (2M). The phases were separated. The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: acetone/iso-hexane ratio 1:9 to 2:8) to give 2-[2-(2,4-dichloro-phenyl)-acetylamino]-nicotinic acid methyl ester as a light yellow gum (197 mg). 1H-NMR (400 MHz, CDCl3): 10.81 (bs, 1H), 8.59-8.60 (m, 1H), 8.29-8.31 (m, 1H), 7.42-7.44 (m, 1H), 7.34-7.36 (m, 1H), 7.23-7.27 (m, 1H), 7.07-7.11 (m, 1H), 4.08 (s, 2H), 3.90 (s, 3H) ppm.

Provenance & Evidence