Cesium fluoride → (S)-cyclopropyl(2-methyl-5-phenoxy-6-(prop-1-ynyl)-3,4-dihydroquinolin-1(2H)-yl)methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.050 g, 0.13 mmol), RuPhos Precatalyst 3rd generation ((2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (0.011 g, 0.01 mmol), cesium fluoride (0.099 g, 0.65 mmol), and tributyl(prop-1-ynyl)stannane (0.107 g, 0.32 mmol) in 1,4-dioxane (4 mL) was heated with microwave irradiation for 1 h at 160° C. The reaction mixture was cooled to room temperature, passed through a short pad of Celite and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 1:5, ethyl acetate/petroleum ether). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5 um, 19×100 mm; mobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (50% to 100% acetonitrile in 10 min, flow rate: 20 mL/min); Detector: UV 220&254 nm. This afforded (S)-cyclopropyl(2-methyl-5-phenoxy-6-(prop-1-ynyl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.011 g, 26%) as a light brown semi-solid. 1H NMR (400 MHz, CD3OD) δ ppm 0.65-0.85 (m, 1H), 1.02-0.87 (m, 2H), 1.03-1.22 (m, 4H), 1.37-1.51 (m, 1H), 1.82 (s, 3H), 1.88-2.03 (m, 1H), 2.07-2.42 (m, 2H), 2.58-2.82 (m, 1H), 4.85-4.72 (m, 1H), 6.78 (d, J=7.80 Hz, 2H) 7.00 (t, J=7.50 Hz, 1H), 7.25-7.31 (m, 4H). MS (ESI, pos. ion) m/z 346 [M+H]+.

Provenance & Evidence