N,N,N',N'-Tetramethylethylenediamine → Benzyl [(3S)-1-(3-cyano-5-nitropyridin-4-yl)piperidin-3-yl]carbamate

Temperatur

140 °C

A mixture of benzyl [(3S)-1-(3-bromo-5-nitropyridin-4-yl)piperidin-3-yl]carbamate (0.082 g, 0.19 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.0097 g, 0.0094 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.0109 g, 0.0188 mmol), zinc cyanide (0.066 g, 0.56 mmol), N,N,N′,N′-tetramethylethylenediamine (0.0114 mL, 0.0755 mmol) in DMF (1.40 mL) was in a vial was deoxygenated. The vial was purged with nitrogen several times, then sealed. The reaction mixture was heated in the sealed vial at 140° C. under microwave irradiation for 10 min. After cooling to ambient temperature, the crude reaction mixture was filtered through a pad of diatomaceous earth and the inorganics were washed thoroughly with EtOAc. The filtrate was diluted EtOAc (40 mL) and water (3 mL). The layers were separated and the organic layer was washed with water (3×3 mL). The combined aqueous phases were extracted with EtOAc (3 mL). The combined organic layers were washed with brine (3 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the sub-title compound (0.065 g). The crude product was used without further purification in the subsequent reaction. LCMS (ESI) calc. for C19H20N5O4 [M+H]+: m/z=382.1. found 382.0.

1. customwas deoxygenated
2. customThe vial was purged with nitrogen several times
3. customsealed
4. customunder microwave irradiation for 10 min
5. temperatureAfter cooling to ambient temperature
6. customthe crude reaction mixture
7. filtrationwas filtered through a pad of diatomaceous earth
8. washthe inorganics were washed thoroughly with EtOAc
9. customThe layers were separated
10. washthe organic layer was washed with water (3×3 mL)
11. extractionThe combined aqueous phases were extracted with EtOAc (3 mL)
12. washThe combined organic layers were washed with brine (3 mL)
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-0d70121921164672bdf901438afa1a9a

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09278950B2