反应详情

温度

15 °C

To a solution of 95% NaH (1.82 g, 72.30 mmol) in DMF (100 mL) at 10° C. was added 2-amino-4-hydroxybenzamide (10.0 g, 66.72 mmol) in portions, maintaining the internal temperature at ca. 15° C. The cooling bath was removed, and the solution was allowed to warm to 40° C. over 25 min. The mixture was cooled to 10° C. and a solution of benzyl bromide (7.8 mL, 66.72 mmol) in DMF (20 mL) was added dropwise, and the mixture was allowed to warm to rt. After stirring for 20 h at rt, the mixture was cooled in an ice bath and quenched by addition of aq ammonium chloride. The solution was concentrated and diluted with water. The precipitate was collected by filtration, and the filtrate was extracted with EtOAc. The precipitate from above and the ethyl acetate extracts were combined and chromatographed on silica gel eluting with 20-80% EtOAc/DCM to afford 2-amino-4-(benzyloxy)benzamide as a solid (6.8 g, 43%). 1H NMR (300 MHz, DMSO-d6) δ ppm 5.04 (s, 2 H) 6.14 (dd, J=8.76, 2.54 Hz, 1 H) 6.27 (d, J=2.64 Hz, 1 H) 6.71 (bs, 2 H) 7.26-7.58 (m, 6 H). LC-MS (ESI) m/z 243 (M+H)+.

1. customThe cooling bath was removed
2. temperatureto warm to 40° C. over 25 min
3. temperatureThe mixture was cooled to 10° C.
4. temperatureto warm to rt
5. temperaturethe mixture was cooled in an ice bath
6. customquenched by addition of aq ammonium chloride
7. concentrationThe solution was concentrated
8. additiondiluted with water
9. filtrationThe precipitate was collected by filtration
10. extractionthe filtrate was extracted with EtOAc
11. customchromatographed on silica gel eluting with 20-80% EtOAc/DCM