Cesium carbonate → 4-(3-(4-(Benzyloxy)phenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile

Participants

Reaction Steps

A solution of 4-(3-bromo-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile (29.0 g, 107.4 mmol), 2-(4-(benzyloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (34.7 g, 118.8 mmol), and Cs2CO3 (104.7 g, 322.2 mmol) in toluene (200 mL) and water (50 mL) was degassed. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (8.5 g, 10 mmol) was added under an inert atmosphere and the solution was again degassed. The reaction was then refluxed for 3 h and monitored for completion by TLC. Upon complete consumption of the starting material, the reaction mixture was filtered through a bed of Celite® washing with ethyl acetate. The organic layer was then washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 20% ethyl acetate in n-hexane on 230-400 mesh silica gel (Rf=0.3) to afford 4-(3-(4-(benzyloxy)phenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile (31.5 g, 74.25%) as solid. 1H NMR: 500 MHz, DMSO-d6: δ 7.95 (d, 2H), 7.75 (d, 2H), 7.5 (d, 4H), 7.35 (t, 1H), 7.15 (d, 2H), 7.05 (d, 2H), 5.1 (s, 2H), 1.45 (s, 6H). MS: [M+H]+: m/z=396.0. HPLC: (99.5%, Eclipse XDB-C18, 150×4.6 mm, 5 um. Mobile Phase: 0.1% TFA in Water. (A). ACN (B), Flow rate: 1.5 ml/min).

Provenance & Evidence