反应 #545124

反应方程式

diisopropylethylamine

ethyl chloroformate

2-hydroxy-4-methoxybenzoic acid

2-fluoro-4-bromobenzylamine

diisopropylethylamine

→

3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,31 oxazine-2,4-dione

收率 36.5%

溶剂

ethyl acetate

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   workup.STIRRINGAfter stirring at room temperature for 22 h
2. 2
   洗涤successively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl
3. 3
   干燥The organic layer was dried over Na2SO4
4. 4
   过滤filtered
5. 5
   浓缩concentrated
6. 6
   其他The crude solid was purified by recrystallization with heptane and ethyl acetate

实验过程

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).

来源