Cesium carbonate → tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Temperature

80 °C

To 8-chloro-5H-chromeno[3,4-c]pyridine (0.489 g, 2.247 mmol) (prepared as in Example 5, Part D), (S)-tert-butyl(1-hydroxy-4-methylpentan-2-yl)carbamate (1.474 g, 6.79 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (0.572 g, 1.348 mmol), palladium (II) acetate (0.151 g, 0.674 mmol) and cesium carbonate (1.098 g, 3.37 mmol) was added toluene (4 mL). Nitrogen gas was bubbled through the mixture for 5 min and the mixture heated at 80° C. for 15 h. The reaction mixture was cooled to room temperature and filtered through a bed of celite. Water (10 mL) was added to the filtrate and the product was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine (1×10 mL), dried with sodium sulfate and concentrated under reduced pressure. The residue so obtained was purified by preparative TLC using (50% ethyl acetate in pet ether) to afford tert-butyl(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.4 g, 1.00 mmol, 45% yield) as a semi solid. LCMS (ESI) m/e 399.2 [(M+H)+, calcd for C23H31N2O4 399.5]; LC/MS retention time (Method C): tR=2.16 min.

1. customNitrogen gas was bubbled through the mixture for 5 min
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfiltered through a bed of celite
4. additionWater (10 mL) was added to the filtrate
5. extractionthe product was extracted with ethyl acetate (3×15 mL)
6. washThe combined organic extracts were washed with brine (1×10 mL)
7. dry with materialdried with sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue so obtained
10. customwas purified by preparative TLC

ORD record

ord-e8afde31dc5d4b12a5b66b39799fcab9

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703953B2