Methyl 7-bromo-5-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzo[b]oxepine-4-carboxylate → Methyl 7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate

Participants

Reaction Steps

A solution of 0.4 M (Me)2CuLi was prepared via dropwise addition of methyl lithium in hexanes (1.6 M, 72 mmol, 45 mL) to a suspension of CuI (6.86 g, 36 mmol) in anhydrous diethyl ether (45 mL) in a ice-salt bath. After stirring for 20 min, a homogeneous solution resulted. The solution of dimethyl cuprate was slowly added to a solution of methyl 7-bromo-5-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzo[b]oxepine-4-carboxylate from step H4 (5.1 g, 11.8 mmol) in diethyl ether (40 mL) at −78° C. The mixture was stirred from −78° C. to −40° C. over 2 h. The reaction was quenched with 30 mL of water and the mixture was extracted with diethyl ether (2×200 mL). The combined organic layers were dried over sodium sulfate and concentrated to give methyl 7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate (3.41 g, 11.5 mmol, 97% yield). The crude mixture was used in the next step without purification. 1H NMR (500 MHz, chloroform-d) δ 7.45 (d, J=2.4 Hz, 1H), 7.40 (dd, J=8.5, 2.4 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 4.53 (t, J=6.1 Hz, 2H), 3.84 (s, 3H), 2.54-2.49 (m, 2H), 2.45-2.42 (m, 3H).

Provenance & Evidence