1,2-Dimethoxyethane → 2-(1-(3'-fluoro-4'-(hydroxymethyl)-5'-(methylsulfonyl)biphenyl-4-yl)-2-(2-(2-fluorophenyl)propan-2-yl)-1H-imidazol-4-yl)propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a 50 mL round bottom flask was added 2-(1-(4-bromophenyl)-2-(2-(2-fluorophenyl)propan-2-yl)-1H-imidazol-4-yl)propan-2-ol (380 mg, 911 μmol), DME (25 mL) and H2O (6 mL). The solution was sparged with N2 for 10 min prior to addition of (2-fluoro-6-(methylsulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (360 mg, 1.09 mmol), potassium carbonate (380 mg, 2.73 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (74 mg, 91 μmol). The reaction mixture was allowed to stir at 80° C. for 2 h. The cooled reaction solution was diluted with EtOAc (30 mL) and filtered through a Celite padded Buchner funnel. The filtrate was washed with aq NH4Cl (150 mL×2). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (Biotage SP-1, 25 g SiO2 column, gradient elution from 5% EtOAc to 100% EtOAc) to afford the title compound (100 mg, 20% yield). 1H-NMR (400 MHz, CDCl3) δ 8.02 (d, J=2 Hz, 1H), 7.51 (dd, J1=2 Hz, J2=10 Hz, 1H), 7.29 (d, J=9 2H), 7.08-7.16 (mult, 1H), 6.85-6.92 (mult, 3H), 6.77-6.84 (mult, 2H), 6.65 (s, 1H), 5.09 (d, J=6 Hz, 2H), 3.35 (s, 1H), 3.30 (2, 3H), 3.02 (t, J=6 Hz, 1H), 1.72 (s, 6H), 1.62 (s, 6H); 19F NMR (400 MHz, CDCl3) δ−112.1, −113.5 ppm; LCMS (ES) m/z=541.3 [M+H]+, 563.2 [M+Na]+.

Provenance & Evidence