Potassium Carbonate → 4-Chloro-6,7-dimethoxy-quinoline-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile (from Step B, 20 g, 87 mmol) and POCl3 (87 mL) was heated to reflux and allowed to stir for 2 hours. The reaction mixture was cooled to 70° C. and concentrated in vacuo to provide a crude residue. The crude residue was diluted with methylene chloride and the resultant solution was cooled to 0° C. and to the resultant solution was added aqueous K2CO3 until the solution was at pH 8-9. The resultant solution was allowed to stir for 30 minutes at 25° C., then transferred to a separatory funnel. The organic layer was collected, washed with water, dried over sodium sulfate, filtered through celite, and concentrated in vacuo to provide 4-chloro-6,7-dimethoxyquinoline-3-carbonitrile as an off-white solid (19.8 g, 92%). A sample recrystallized from methylene chloride was characterized as follows: mp 220-223° C.; 1H NMR (DMSO-d6)δ 8.98 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 4.02 (s, 3H), 4.01 (s, 3H).

Provenance & Evidence