Cesium carbonate → 4-methoxy-5-styryl-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

Participants

Reaction Conditions

Reaction Steps

A 1 L three-necked round bottom flask fitted with an overhead stirrer was dried and cooled under a stream of nitrogen then charged with 5-bromo-4-methoxy-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (30 g, 0.096 mol, 1.0 equiv.) in 1,4-dioxane (300 mL) and water (60 mL). The mixture was degassed with nitrogen. To the degassed solution at RT was added sequentially trans-β-styrene boronic acid (14.26 g, 0.096 mol, 1.0 equiv.), Cs2CO3 (62.82 g, 0.19 mol, 2.0 equiv.), Pd(II)Cl2(PPh3)2 (3.38 g, 0.004 mol, 0.05 equiv.) then the reaction was heated with stirring at 100° C. for 6 h. The reaction mixture was quenched with ice cold water (1 L) and extracted with EtOAc (2×1 L). The organic layers were combined, washed with brine solution (500 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (40-50% EtOAc) to afford 4-methoxy-5-styryl-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (25 g, 77%) as a brown solid.

Provenance & Evidence