Triethylborane → HCID 68904762, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of toluene (17 mL) and 2 M aqueous sodium carbonate (5 mL) was degassed by bubbling nitrogen for 20 minutes. To the mixture was added 4-chloro-6-methoxy-quinoline (500 mg, 2.58 mmol) and tetrakis(triphenylphosphine)palladium(0) (90 mg, 0.0774 mmol), followed by 1 M triethylborane solution in hexane (15.5 mL, 15.5 mmol). The reaction mixture was stirred at 90° C. for 4 days, periodically adding more palladium catalyst (270 mg total) and triethylborane solution (30 mL total) to drive the reaction. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, and adsorbed on silica gel. Purification by flash chromatography using a gradient of 0-70% ethyl acetate/hexane afforded 579 mg of impure 4-ethyl-6-methoxy-quinoline as a waxy off white solid. The solid was treated with concentrated sulfuric acid (6 mL) and water (4 mL). The reaction mixture was stirred at reflux for 5 h and poured onto ice. Ammonium hydroxide was added until pH 9 and the aqueous layer was extracted with ethyl acetate (2×). Combined organics were adsorbed on silica gel. Purification by flash chromatography using a gradient of 0-80% ethyl acetate/hexane afforded 195 mg of 4-ethyl-quinolin-6-ol as an off white solid (44% yield): 1H NMR (DMSO-d6) δ 1.30 (t, 3H), 2.96 (q, 2H), 7.25 (d, 1H), 7.28 (m, 2H), 7.86 (d, 1H), 8.56 (d, 1H), 9.98 (broad s, 1H); MS (m/z) 174 [M+H]+.

Provenance & Evidence