Hydrochloric Acid → Ethyl 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Phosgene (51 g, 0.52 mol) dissolved in 150 ml of dioxane was added in portions to a mechanically stirred slurry of 2-amino-6-chloro-benzoic acid (30 g, 0.175 mol) and sodium bicarbonate (44 g, 0.52 mol) in 300 ml of dioxane. Violent reaction with gas evolution occurred and the reaction mixture was cooled to keep the temperature below 50° C. Then stirring was continued at 50° C. for 1 hour. The reaction mixture was cooled to 15° C., the resulting precipitate was collected, washed with water and dried to give the isatoic anhydride. The anhydride (5 g, 0.025 mol) was dissolved in 50 ml of N,N-dimethylacetamide and cooled to 0° C. Sodium hydride (75%) (0.94 g, 0.028 mol) and then methyl iodide (1.89 ml, 0.030 mol) was added at a rate to keep the temperature below 5° C. The reaction mixture was stirred at room temperature for 5 hours. The remaining methyl iodide was removed uuder vacuum. Sodium hydride (0.94 g, 0.028 mol) was added together with diethyl malonate (4.5 g, 0.028 mol). The mixture was heated at 85° C. for 5 hours. After cooling to room temperature, 50 ml of methanol and 50 ml of 1 M hydrochloric acid and subsequently 250 ml of water were added. An emulsion was formed which crystallised on standing in a refrigerator for 72 hours. The crystalline mass was collected by filtration, washed with water, water/methanol (1:1) and heptane and dried to afford the title compound (6.3 g), yield 74%.

Provenance & Evidence