反应详情

To a solution of 4-chloro-2-phenylamino-benzoic acid (10.1 g, 41.0 mmol) in DMF (200 mL) was added O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluorophosphate (HBTU, 31.2 g, 82.0 mmol), N,O-dimethyl-hydroxylamine hydrochloride (7.94 g, 82.0 mmol), and N,N-diisopropylethylamine (45.0 g, 350.0 mmol) at room temperature. The resulting mixture was stirred for 24 hr. at room temperature. Completion of the reaction was confirmed by silica TLC (mobile phase; hexane:ethyl acetate=7:3; Rf=0.5). The reaction mixture was diluted with ethyl acetate (600 mL) and the organic layer was washed with water (4×200 mL) and brine (200 mL). The organic layer was dried over anhydrous Na2SO4 and volatiles were removed under reduced pressure. The crude material was purified over silica gel (100-200 mesh) column chromatography, using gradient polarity mobile phase (ethyl acetate:hexane=1:9-1:4), to give 4-chloro-N-methoxy-N-methyl-2-phenylamino-benzamide (6.62 g, 56.4% yield) as a yellow solid. 1H NMR (DMSO-d6) δ ppm 7.93 (s, 1H) 7.20-7.39 (m, 3H) 7.02-7.17 (m, 3H) 6.88-6.99 (m, 2H) 3.50 (s, 3H) 3.20 (s, 3H). MS calcd. for C15H15ClN2O2 [(M+H)+] 291.0, obsd. 291.0, [(M-C2H6NO)+] 230.0, obsd. 230.0.

1. customat room temperature
2. washthe organic layer was washed with water (4×200 mL) and brine (200 mL)
3. dry with materialThe organic layer was dried over anhydrous Na2SO4 and volatiles
4. customwere removed under reduced pressure
5. customThe crude material was purified over silica gel (100-200 mesh) column chromatography