Diethyl Ether → HCID 25115597, compound

Participants

Reaction Conditions

Reaction Steps

To tetrahydrofuran (2.0 mL) cooled to −20° C. a solution of n-butyllithium 2.5 M in hexane (0.644 mL, 1.61 mmol) was added via syringe. After 5 min diisopropylamine (0.227 mL, 1.61 mmol) was added and the reaction mixture was stirred for 15 min at that temperature and then cooled down to −78° C. A solution of 3,6-dimethoxypyridazine (0.098 g, 0.7 mmol) in tetrahydrofuran (2.0 mL) was added and the reaction mixture was stirred for 1 h at −78° C. Zinc chloride 1.0 M solution in diethylether (1.610 mL, 1.61 mmol) was added and the reaction mixture was allowed to warm up to ambient temperature. A solution of (3S)-3-(Dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonate (0.368 g, 0.77 mmol) in tetrahydrofuran (2.0 mL) and tetrakis(triphenylphosphine)palladium(0) (0.032 g, 0.03 mmol) were added and the reaction mixture was heated to reflux for 16 hours. The reaction mixture was diluted with ethyl acetate and added saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate, concentrated in vacuo and purified by column chromatography using a gradient of ethyl acetate in heptane yielding 0.235 g (72%) of the desired compound as a colorless oil; 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.36 (m, 8 H), 7.19-7.25 (m, 2 H), 7.15 (t, 1 H), 6.87 (dd, 1 H), 6.81 (s, 1 H), 6.71 (dd, 1 H), 4.34 (dd, 1 H), 4.14 (s, 3 H), 4.04-4.09 (m, 1 H), 4.03 (s, 3 H), 3.69 (s, 4 H), 3.23 (br. s., 1 H), 2.29-2.99 (m, 2 H); MS (APPI/APCI) m/z 468[M+H+].

Provenance & Evidence