1,4,7,10-Tetraoxacyclododecane → 2-chloro-5-cyano-N,N-dimethylnicotinamide

Temperatur

40 °C

A mixture of 2-chloro-5-iodo-N,N-dimethylnicotinamide (1.54 g, 5 mmol), prepared as in Example 14, and lithium cyanide (0.5M in DMF, 20 mL, 10 mmol) was distilled at reduced pressure. The residue was suspended in 1,4,7,10-tetraoxacyclo-dodecane (0.2 mL, 1.25 mmol) in 50 mL of benzene and the mixture was distilled under nitrogen until a forefraction of approximately 5 mL had collected. The suspension was allowed to cool and then tetrakis(triphenylphosphine)palladium(0) (2.44 g, 2.1 mmol) was added. The mixture was stirred at 40° C. under nitrogen for 1 week, allowed to cool to room temperature and partitioned between aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with diethyl ether and the extract was washed with brine, dried (Na2 SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (5:1) to give 2-chloro-5-cyano-N,N-dimethylnicotinamide (0.57 g, 2.72 mmol), m.p. 148°-153° C.

1. distillationwas distilled at reduced pressure
2. distillationthe mixture was distilled under nitrogen until a forefraction of approximately 5 mL
3. customhad collected
4. temperatureto cool
5. temperatureto cool to room temperature
6. custompartitioned between aqueous sodium bicarbonate and ethyl acetate
7. extractionThe aqueous layer was extracted with diethyl ether
8. washthe extract was washed with brine
9. customdried (Na2 SO4)
10. concentrationconcentrated
11. customThe residue was purified on silica gel by column chromatography
12. washeluting with hexanes/ethyl acetate (5:1)

ORD-Eintrag

ord-aa35a15c97f14838b8be959e195efa38

Quelldatensatz

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05688795