Dimethylformamide → 4-Methylpyrimidine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloro-4-methylpyrimidine (1 g, 7.78 mmol) and zinc cyanide (475 mg, 4.04 mmol) in anhydrous DMF (10 ml) was added Pd(PPh3)4 (449 mg, 0.366 mmol) and nitrogen flushed through the mixture for 5 min. The mixture was heated at 180° C. for 30 min in a microwave reactor. The reaction was repeated on the same scale and the reaction mixtures were combined. The mixture was partitioned between EtOAc and water (filtered through celite to remove some insolubles), and the organic layer washed with sat. NaCl, dried over MgSO4, filtered and evaporated. The residue was purified by MPLC (Biotage Horizon: FLASH 25+M) eluent: 100% Hexanes (90 ml), gradient rising from 100% Hexanes to 15% EtOAc in Hexanes (900 ml), then 15% EtOAc in Hexanes (500 ml) to give 1 g of the title compound (54%) as an off-white solid. 1H NMR (CDCl3): 2.62 (s, 3H), 7.42 (d, J5.1 Hz, 1H), 8.69 (d, J5.1 Hz, 1H).

Provenance & Evidence