反应详情

To a 0° C. mixture of diisopropylethylamine (34.36 mL, 197.25 mmol) and O,N-dimethyl-hydroxylamine hydrochloride (19.24 g, 197.25 mmol) in CHCl3 (300 mL) was added 2-amino-5-fluorobenzoic acid (25.50 g, 164.38 mmol) followed by EDC (31.51 g, 164.38 mmol). The reaction was stirred from 0° C. to ambient temperature over 2 h and then diluted with CH2Cl2 (100 mL), washed with saturated sodium bicarbonate solution (100 mL) and brine (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (3-8% MeOH/CH2Cl2) yielded 2-amino-5-fluoro-N-methoxy-N-methylbenzamide as a yellow oil. 1H NMR (CDCl3, 400 MHz) 7.12 (m, 1H, ArH); 6.93 (m, 1H, ArH); 6.65 (m, 1H, ArH); 3.63 (s, 3H, CH3); 3.35 (s, 3H, CH3); MS (Electrospray): m/z 199.1 (M+H).

1. washwashed with saturated sodium bicarbonate solution (100 mL) and brine (100 mL)
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customPurification by normal phase chromatography (3-8% MeOH/CH2Cl2)