Phenyl isocyanate → 5-(4-bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazole

Temperatur

100 °C

To a flask containing a solution of 4-bromo-1-ethynyl-2-methylbenzene (875 mg, 4.49 mmol) (may be prepared according to the procedures in Journal of Chemical Research (2007), 12 728-732) in toluene (20 mL), was added 2-(2-nitroethoxy)tetrahydro-2H-pyran (1.34 g, 7.63 mmol), phenyl isocyanate (1.82 g, 15.3 mmol), and triethylamine (1.50 mL, 10.8 mmol). The reaction was heated at 100° C. and stirred under nitrogen overnight. The reaction was cooled, quenched with methanol and filtered. The filtrate was evaporated in vacuo onto silica gel. Chromatography on silica gel with a heptane-ethyl acetate gradient (0-35% ethyl acetate) eluted 5-(4-bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazole as an orange oil (581 mg, 36.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.57-1.71 (m, 4H) 1.73-1.82 (m, 1H) 1.82-1.91 (m, 1H) 2.51 (s, 3H) 3.56-3.62 (m, 1H) 3.89-3.96 (m, 1H) 4.69 (d, J=12.88 Hz, 1H) 4.76-4.79 (m, 1H) 4.86 (d, J=12.88 Hz, 1H) 6.51 (s, 1H) 7.42-7.46 (m, 1H) 7.48 (d, J=1.56 Hz, 1H) 7.59 (d, J=8.20 Hz, 1H).

1. custommay be prepared
2. temperatureThe reaction was cooled
3. customquenched with methanol
4. filtrationfiltered
5. customThe filtrate was evaporated in vacuo onto silica gel
6. washChromatography on silica gel with a heptane-ethyl acetate gradient (0-35% ethyl acetate) eluted 5-(4-bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazole as an orange oil (581 mg, 36.8%)

ORD-Eintrag

ord-8889b859bc844c9789821c342b212155

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09018384B2