反应详情

温度

60 °C

In a flask at room temperature, was added 2-amino-3-cyclopropoxybenzoic acid (6.61 g, 34.2 mmol) N,O-dimethylhydroxylamine hydrochloride (10.01 g, 103 mmol), N-ethyl-N″-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.87 g, 41.1 mmol) and 1-hydroxybenzotriazole hydrate (6.29 g, 41.1 mmol) in 50 ml of DMF. To the solution was added triethylamine (19.07 mL, 137 mmol). The reaction solution was stirred at 60° C. overnight and then cooled to room temperature. The reaction mixture was partitioned between water and ethyl acetate and transferred to a separatory funnel and washed with 10% LiCl, water, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to provide dark oil. The crude product mixture was purified via ISCO (0%-50% of EtOAC/DCM in 15 minutes, 120 g column) to give 2-amino-3-cyclopropoxy-N-methoxy-N-methylbenzamide (5.2 g, 22.01 mmol, 64.3% yield). HPLC: RT=1.975 min (H2O/MeOH with TFA, SunFire C18 3.5 μm, 2.1×30 mm, gradient=4 min, wavelength=220 nm); MS(ES):m/z=237.12 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ 7.17 (dd, J=8.0, 1.2 Hz, 1H), 7.02 (dd, J=7.9, 1.3 Hz, 1H), 6.67 (t, J=7.9 Hz, 1H), 4.78 (br. s., 2H), 3.88-3.73 (m, 1H), 3.69-3.56 (m, 3H), 3.36 (s, 3H), 0.92-0.72 (m, 4H)).

1. temperaturecooled to room temperature
2. customThe reaction mixture was partitioned between water and ethyl acetate
3. customtransferred to a separatory funnel
4. washwashed with 10% LiCl, water, and brine
5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto provide dark oil
9. customThe crude product mixture was purified via ISCO (0%-50% of EtOAC/DCM in 15 minutes, 120 g column)