2,6-Di-tert-butyl-4-methylphenol → 8-bromo-5H-chromeno[3,4-c]pyridine

Temperature

140 °C

A solution of (E)-2-((E)-3-(4-bromo-2-(prop-2-ynyloxy)phenyl)allylidene)-1,1-dimethylhydrazine (116 mg, 374 mmol) and 2,6-di-tert-butyl-4-methylphenol (82 mg, 374 mmol) in mesitylene (4.5 mL) was degassed at 50° C. by bubbling argon for ˜15 min while sonicating in a thick glass vial. The vial was capped under argon and heated to 140° C. in an oil bath with stirring for 138 h (5.75 days). The reaction mixture was cooled to ambient temperature and the solvent was concentrated under reduced pressure. The dark residue was purified by silica gel chromatography with EtOAc:dichloromethane (1:19) as the eluant. Fractions containing the required product were combined and concentrated under reduced pressure to give 8-bromo-5H-chromeno[3,4-c]pyridine (27 mg, 0.088 mmol, 25% yield based on 89% purity) as a pale yellow powder. 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J=5.2 Hz, 1H), 8.45 (s, 1H), 7.62 (d, J=8.2 Hz, 1H), 7.52 (d, J=5.2 Hz, 1H), 7.27-7.22 (m, 2H), 5.20 (s, 2H); LCMS (Method A) (ESI) m/e 262.0, 264.0 Br pattern [(M+H)+, calcd for C14H15BrN2O 262.0].

1. customby bubbling argon for ˜15 min
2. customwhile sonicating in a thick glass vial
3. customThe vial was capped under argon
4. temperatureThe reaction mixture was cooled to ambient temperature
5. concentrationthe solvent was concentrated under reduced pressure
6. customThe dark residue was purified by silica gel chromatography with EtOAc:dichloromethane (1:19) as the eluant
7. additionFractions containing the required product
8. concentrationconcentrated under reduced pressure

ORD record

ord-dfaf8338f976415ea284b3b0f0244b74

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2