Potassium Carbonate → methyl 7-(4-(4-methoxyphenyl)-1H-imidazol-1-yl)-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

To an oven dried microwave vial was added methyl 7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate from step H5 (200 mg, 0.673 mmol), 4-(4-methoxyphenyl)-1H-imidazole (141 mg, 0.808 mmol), potassium carbonate (186 mg, 1.35 mmol) and copper(I) iodide (72.9 mg, 0.383 mmol). The vial was capped with a septum and the system was degassed and flushed with nitrogen (3×). Then 2,2,6,6-tetramethylheptane-3,5-dione (0.194 mL, 0.944 mmol) and DMF (5 mL) were added and the reaction mixture was degassed and flushed with nitrogen (3×). The vial was sealed and place in a pre-heated oil bath at 120° C. The reaction mixture was stirred at 120° C. for 20 h. The reaction was poured into water to afford a blue mixture that was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography (30-100% EtOAc/hexanes) to afford methyl 7-(4-(4-methoxyphenyl)-1H-imidazol-1-yl)-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate (180 mg, 0.461 mmol, 69% yield). LCMS (M+H)+=391.1. 1H NMR (500 MHz, chloroform-d) δ 7.88 (br. s., 1H), 7.77 (d, J=7.2 Hz, 2H), 7.39-7.33 (m, 3H), 7.18 (d, J=8.4 Hz, 1H), 6.94 (d, J=7.5 Hz, 2H), 4.59 (t, J=6.0 Hz, 2H), 3.87-3.82 (m, 6H), 2.57 (t, J=5.9 Hz, 2H), 2.49 (s, 3H).

Provenance & Evidence