2-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline → 5-(5,5-Dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile

Participants

Reaction Steps

A solution of 5-(3-bromo-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile (0.15 g, 0.465 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.17 g, 0.465 mmol), and Cs2CO, (0.75 g, 2.32 mmol) in toluene (6 mL) and water (3 mL) was degassed. Then, Pd(dppf)Cl2 (0.76 g, 0.090 mmol) was added under an inert atmosphere and the solution was again degassed. The reaction was then refluxed for 2 h, filtered through a pad of Celitc® and the filtrate was diluted with EtOAc (40 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 5-(5,5-dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile (125 mg, 58%) as a pale yellow solid. 1H NMR (500 MHz, d6-DMSO): δ 8.43 (d, J=8.5 Hz, 1H), 8.02 (t, J=7.9 Hz, 2H), 7.90 (s, 1H), 7.81-7.77 (m, 2H), 7.70 (d, J=8.2 Hz, 1H), 7.62 (t, J=8.2 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 7.19 (d, J=7.4 Hz, 2H), 7.12 (d, J=7.5 Hz, 2H), 5.40 (s, 2H), 3.95 (s, 3H), 1.46 (s, 6H). MS: [M+Na]: m/z=499.3, [M+H]: m/z=477.2. HPLC: 98%, Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), AcN (B), Flow rate: 0.5 ml/min (Gradient).

Provenance & Evidence