Nitric Acid → N-(4-Imidazol-1-yl-2-methyl-6-nitro-phenyl)-acetamide

To a solution of 4-imidazol-1-yl-2-methyl-phenylamine (1 g, 5.78 mmol) in CH2Cl2 (20 mL) was added Ac2O (0.7 mL, 7.28 mmol) at 0° C. The reaction mixture was stirred at room temperature for 14 h and diluted with water. The aqueous layer was extracted with CH2Cl2 and the combined organic layers were washed with saturated NaHCO3 and brine, dried over Na2SO4, and concentrated in vacuo to give a white solid. The white solid was suspended in H2SO4 (conc.) (15 μL). Then HNO3 (conc.) (0.312 mL) was added to the suspension at 0° C. The reaction mixture was slowly warmed to room temperature and stirred at room temperature for 4 h. After cooling to −10° C., the reaction mixture was neutralized with ammonium hydroxide extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography (1:9:5 MeOH/THF/hexane) to yield the title compound (0.61 g, 41%). 1H NMR (300 MHz, CD3OD) δ 8.11 (1H, s), 7.45-7.56 (2H, m), 7.38 (1H, dd, J=2.4, 8.4 Hz), 7.14 (1H, s), 2.33 (3H, s), 2.18 (3H, s).

1. extractionThe aqueous layer was extracted with CH2Cl2
2. washthe combined organic layers were washed with saturated NaHCO3 and brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated in vacuo
5. customto give a white solid
6. temperatureThe reaction mixture was slowly warmed to room temperature
7. stirringstirred at room temperature for 4 h
8. temperatureAfter cooling to −10° C.
9. extractionextracted with ethyl acetate
10. washThe combined organic layers were washed with brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customThe residue was purified by flash chromatography (1:9:5 MeOH/THF/hexane)

ORD record

ord-2603561f7da44821bc73588ac2c8dfd0

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07312215B2