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

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Reaction Conditions

Reaction Steps

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.

Provenance & Evidence