Potassium Carbonate → HCID 178494373, compound

Participants

Reaction Conditions

Reaction Steps

In a dry round bottom flask charged with 2-hydroxyquinoline-3-carboxylic acid (528 mg, 2.8 mmol) was added thionyl chloride (4 mL, 57 mmol). The mixture was then heated to reflux for 20 minutes before rotary evaporation of the thionyl chloride. In a separate flask amine 5 (430 mg, 2.3 mmol) was dissolved in anhydrous tetrahydrofuran (17 mL) and cooled to −78° C. under an inert nitrogen atmosphere. To the cooled amine solution was slowly added lithium tert-butoxide (in 1 M tetrahydrofuran; 3 mL, 3 mmol) followed by stirring for 15 minutes. The acid chloride was then suspended in tetrahydrofuran (12 mL) and directly added to the cooled amine solution. The reaction mixture was stirred overnight, during which time it came to room temperature. The reaction was then diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford 550 mg crude material that contained 10% of the O-aroylated product (as determined by LC-MS). The solid was stirred in 8/1 methanol/water (9 mL) containing 25 mg potassium carbonate for an hour after which it was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution, and brine. The ethyl acetate was dried over anhydrous magnesium sulfate, filtered and concentrated give a solid containing a small amount of the ester. The product was then purified over a small plug of silica, eluting with 95/5 dichloromethane/ethyl acetate to give 530 mg of a pale yellow solid (64% yield). The product structure was confirmed by 1H NMR. NMR (CDCl3): δ12.30 (br.s, 1H), 10.60 (br.s, 1H), 9.00 (m, 1H), 7.80 (m, 1H), 7.65 (m, 1H), 7.40 (m, 2H), 5.60 (m, 1H), 3.85 (m, 1H), 3.70 (s, 3H), 3.50 (m, 1H), 3.40 (s, 3H) ppm.

Provenance & Evidence