4-Nitrophenol → 5-Methyl-3-(4-nitrophenoxymethyl)isoxazole

To a dry reaction flask equipped with a reflux condenser, a magnetic stirring bar and a rubber septum with a N2 inlet was placed 4-nitrophenol (2, X═H) (1.57 g, 11.36 mmol), anhydrous K2CO3 (1.58 g, 12 mmol) and tetrabutylammonium iodide (200 mg) in dry acetone (100 mL). The reaction mixture was stirred at room temperature for 30 minutes. To this heterogeneous mixture was added 3-(bromomethyl)-5-methylisoxazole (2.0 g 11.36 mmol) at room temperature and then the reaction mixture was refluxed for over night. After cooling it to room temperature, the reaction mixture was filtered, washed with acetone (50 mL) and the combined filtrates were concentrated under reduced pressure. The resulting solid was purified by silica gel column, eluted with hexanes then polarity was increased gradually up to 40% EtOAc in hexanes to give 2.59 g (97%) of the desired 5-methyl-3-(4-nitrophenoxymethyl)isoxazole (3, X═H). 1H NMR (CDCl3): δ 8.19 (d, 2H, J=9.3 Hz), 7.04 (d, 2H, J=9.6 Hz), 6.18 (s, 1H), 5.20 (s, 2H), 2.44 (s, 3H); LCMS (m/z): 235 (MH+).

1. customTo a dry reaction flask
2. customequipped with a reflux condenser, a magnetic stirring bar
3. customa rubber septum with a N2 inlet was placed
4. temperaturethe reaction mixture was refluxed for over night
5. temperatureAfter cooling it to room temperature
6. filtrationthe reaction mixture was filtered
7. washwashed with acetone (50 mL)
8. concentrationthe combined filtrates were concentrated under reduced pressure
9. customThe resulting solid was purified by silica gel column
10. washeluted with hexanes
11. temperaturewas increased gradually up to 40% EtOAc in hexanes

ORD record

ord-7057dd5b010044cdb2d9f5915b3ce0d0

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415365B2