Dimethylacetamide → 6-Chloro-2-methylpyrimidine-4-carbonitrile

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Reaction Steps

The 4,6-dichloro-2-methyl-pyrimidine (10 g, 60 mmol), palladium (II) trifluoroacetate (0.86 g, 2.6 mmol), zinc dust (65.3 g, 11.4 mmol), rac-2-(di-t-butylphosphino)-1,1-binaphthyl (2.1 g, 5.3 mmol), zinc cyanide (3.95 g, 33.7 mmol) and dimethyl acetamide (316 ml) were added to a 500 mL, flame-dried flask. The vessel was evacuated and back-filled with N2 (3×). The mixture was stirred under N2 for 30 min. at RT, then heated to 95° C. After 2.5 hours the mixture was diluted with EtOAc (300mL), and washed with water (300 mL×3). The organic fractions were combined, dried over MgSO4, filtered, and the volatiles removed in vacuum. The residue was dissolved in EtOAc (100 mL), washed with water (50 ml), and the layers separated. The aqueous phase was then extracted with EtOAc (50 mL), the organic fractions combined, dried over MgSO4, filtered, and the volatiles removed in vacuum. The crude mixture was purified by chromatography on silica gel (eluting 1:19 ethyl acetate:hexane) to yield the titled compound as a colorless oil. 1H NMR (CD3OD): 8.235 (s, 1H), 2.816 (s, 3H).

Provenance & Evidence