Ethyl chloroformate → 3-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione

참여 물질

반응 단계

A solution of 2-hydroxy-4-methoxybenzoic acid (2.04 g, 12.2 mmol) in tetrahydrofuran (20 mL, 0.6 M)was cooled to 0° C. After being treated with diisopropylethylamine (4.4 mL, 25.3 mmol), and ethyl chloroformate (2.4 mL, 25.1 mmol), the mixture was stirred at room temperature for 1 h and subsequently treated with a solution of 2-fluoro-4-bromobenzylamine (2.92 g, 12.1 mmol) and diisopropylethylamine (4.4 mL, 25.3 mmol) in tetrahydrofuran (15 mL). After stirring at room temperature for 22 h, the reaction mixture was diluted ethyl acetate and successively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The crude solid was purified by recrystallization with heptane and ethyl acetate to give 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,31 oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) δ 7.87 (d, J=8.4 Hz, 1 H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1 H), 7.33–7.34 (m, 2 H), 7.03–6.99 (m, 2 H), 5.02 (s, 2 H), 3.87 (s, 3 H).

출처 및 근거