Cesium carbonate → Phthalimide

Temperature

80 °C

To a stirred suspension of 8-chloro-5-vinyl-5H-chromeno[3,4-c]pyridine (0.2 g, 0.821 mmol), (5)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione (0.609 g, 2.462 mmol), 2-di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (0.209 g, 0.492 mmol), and cesium carbonate (0.401 g, 1.231 mmol) in toluene (25 mL) was added palladium (II) acetate (0.055 g, 0.246 mmol). Nitrogen gas was bubbled through the mixture for 5 min, and then the reaction mixture was heated to 80° C. for 14 h. The reaction was diluted with ethyl acetate (25 mL) and filtered through celite. The filtrate was washed with water (1×20 mL) and brine (1×20 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes) to afford 24(2S)-4-methyl-1-(5-vinyl-5H-chromeno[3,4-c]pyridin-8-yloxy)pentan-2-yl)isoindoline-1,3-dione (0.3 g, 0.660 mmol, 40% yield for three steps). LCMS (ESI) m/e 455.2 [(M+H)+, calcd for C28H27N2O4 455.2]; LC/MS retention time (Method C): tR=2.16 min.

1. customNitrogen gas was bubbled through the mixture for 5 min
2. additionThe reaction was diluted with ethyl acetate (25 mL)
3. filtrationfiltered through celite
4. washThe filtrate was washed with water (1×20 mL) and brine (1×20 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes)

ORD record

ord-34677cecbd1f4bceabcb6e7a94cbaa0a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2