Ethyl Acetate → HCID 66616497, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of dimethyl 5-bromoisophthalate (5.47 g, 20.03 mmol), 4-fluorophenylboronic acid (4.20 g, 30.0 mmol) and cesium carbonate (9 g, 27.6 mmol) in dioxane (60 mL) was purged with Ar gas for a few minutes, to the mixture was added Pd(PPh3)4 (1 g, 0.865 mmol). The reaction mixture was heated at 90° C. overnight. The next morning additional Pd-catalyst (˜300 mg) was added, and the reaction mixture was heated at 90° C. for an additional 7 h. To the reaction mixture was added EtOAc and water, and the insoluble material was filtered. The EtOAc layer was separated, dried over MgSO4, concentrated in vacuo and the residual solid was mixed with ether. The insoluble solid was filtered and the filtrate was concentrated. To the residue was added ether, the insoluble solid was filtered (this solid was mostly boronic acid) and the filtrate solution was concentrated. The residue was purified by flash column chromatography on SiO2 which provided a mixture of desired product and dimethyl 5-bromoisophthalate (3.4 g). This mixture was carried on into the same coupling reaction again repeating the same procedure except it was heated at 77° C. for 16 h. The solid was filtered, washed with EtOAc, and the filtrate solution was washed with water, dried, concentrated, and the residue was passed through a flash column on SiO2 eluting with 3:1/Hex:EtOAc, which provided the desired product (3.0 g, 10.41 mmol, 52%) as a white solid. 1H NMR (CDCl3): δ 8.62 (d, J=1.7 Hz, 1H), 8.39 (d, J=1.7 Hz, 2H), 7.61 (dd, J=8.8, 5.5 Hz, 2H), 7.15 (t, J=8.8 Hz, 2H), 3.96 (s, 6H).

Provenance & Evidence