반응 #610402

반응 방정식

HCl

3-bromo-2-methylaniline

6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione

trimethylaluminum

→

2-amino-N-(3-bromo-2-methylphenyl)-5-fluorobenzamide

수율 34.3%

용매

toluene

toluene

반응 조건

후처리

1. 1
   온도was cooled on an ice-water bath
2. 2
   온도was heated at 70° C. overnight
3. 3
   온도The mixture was cooled to 0° C.
4. 4
   추출extracted 3 times with EtOAc
5. 5
   세척The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water
6. 6
   기타dried
7. 7
   농축concentrated
8. 8
   세척eluting with EtOAc-hexanes (gradient from 5-40%)

실험 절차

A mixture of 3-bromo-2-methylaniline (1.50 g, 8.06 mmol) and 6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (1.46 g, 8.06 mmol) in toluene (40 mL) was cooled on an ice-water bath and treated portionwise with 2 M trimethylaluminum in toluene (10.1 mL, 20.2 mmol). The mixture was stirred at room temperature for 30 min, then was heated at 70° C. overnight. The mixture was cooled to 0° C., carefully treated with 1M aqueous HCl, and extracted 3 times with EtOAc. The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water, dried and concentrated. The residue was subjected to column chromatography on silica gel (120 g), eluting with EtOAc-hexanes (gradient from 5-40%), to provide 2-amino-N-(3-bromo-2-methylphenyl)-5-fluorobenzamide (0.893 g, 87% purity, 30% yield). Mass spectrum m/z 323, 325 (M+H)+. 1H NMR (400 MHz, MeOH-d4) δ 7.54 (1H, dd, J=8.03, 0.99 Hz), 7.48 (1 H, dd, J=9.68, 3.08 Hz), 7.33 (1 H, d, J=7.26 Hz), 7.16 (1 H, t, J=7.92 Hz), 7.04-7.12 (1 H, m), 6.83 (1 H, dd, J=9.02, 4.62 Hz), 2.39 (3 H, s).

출처