Diethyl (ethoxymethylene)malonate → Ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate

Temperature

27.5 °C

Hydrazine hydrate (1.7 g) was added dropwise over 30 min to a stirred suspension of 5% Rh—C (wet, 110 mg) and nitrobenzene (4.1 g) in THF (20 mL) at 15° C. controlled by ice-bath. The reaction mixture was warmed to 25-30° C. for 2 h, followed by filtration. The filtrate was diluted with an equal volume of dichloromethane, dried over sodium sulfate, then condensed to a small volume. Addition of petroleum ether to this solution led to the formation of a needle-like white solid as the fairly pure product of phenyl hydroxyamine (3.2 g, 86%). The reaction mixture of phenyl hydroxyamine (2.675 g, 25 mmol), diethyl ethoxymethylene malonate (4.324 g, 20 mmol) and ethanol (20 mL) was stirred at RT for 12 h to form a large amount of solid, which after warming on a water-bath for 3 h disappeared and reappeared when the reaction mixture was cooled down to RT. Filtration and washing with ethanol provided the title compound as white crystal like solid (4.25 g, 91%). 1H NMR (200 MHz, CDCl3) δ (ppm): 8.40 (s, 1H), 7.46-7.28 (m, 5H), 4.23(q, J=7.1 Hz, 2H). 1.31 (t, J.=7.1 Hz, 3H).

1. customcontrolled by ice-bath
2. filtrationfollowed by filtration
3. additionThe filtrate was diluted with an equal volume of dichloromethane
4. dry with materialdried over sodium sulfate
5. customcondensed to a small volume
6. customto form a large amount of solid, which
7. temperatureafter warming on a water-bath for 3 h
8. temperaturewas cooled down to RT
9. filtrationFiltration
10. washwashing with ethanol

ORD record

ord-ce9eb310c265460b9f5b62d38d193b42

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07329651B2