Tetrahydrofuran → 6-bromo-5-methyl-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one

A solution of 3-bromo-6-hydroxy-2-methyl-N-phenylbenzamide (Intermediate 16-1, 50 mg, 0.163 mmol) in THF (2 mL) was treated at rt with lithium aluminum hydride (50 mg, 1.317 mmol) and the mixture was heated at reflux for 2 h. It was then cooled to rt and carefully treated with saturated aqueous ammonium chloride (2 mL). The mixture was diluted with DCM (60 mL) and washed with water (5 mL) and brine (5 mL), dried and concentrated to give the 4-bromo-3-methyl-2-((phenylamino)methyl)phenol (45 mg). Without purification, this material was dissolved in DCM (3 1M) and treated with carbonyldiimidazole (30.5 mg, 0.188 mmol) and DMAP (2.091 mg, 0.017 mmol) at rt and the mixture was stirred for 1 h. The mixture was diluted with DCM (60 mL) and washed with NaHCO3 (aq) (5 mL) and brine (5 mL), dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 95:5 to 50:50 hexane-EtOAc) to give 6-bromo-5-methyl-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one (25 mg). 1H NMR (400 MHz, chloroform-d) δ 7.33-7.57 (6 H, m), 6.88 (1 H, d, J=8.88 Hz), 4.82 (2 H, s), 2.30 (3 H, s). Mass spectrum m/z 318, 320 (M+H)+.

1. temperaturethe mixture was heated
2. temperatureat reflux for 2 h
3. washwashed with water (5 mL) and brine (5 mL)
4. customdried
5. concentrationconcentrated

ORD record

ord-a7586e488a6b42c495faddefaad6f9ce

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362065B2