Dimethylacetamide → 3-Chloro-5-(3-methoxyphenyl)isonicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,5-dichloroisonicotinonitrile (2 g, 11.56 mmol), 3-methoxyphenylboronic acid (1.932 g, 12.72 mmol), potassium phosphate (4.91 g, 23.12 mmol) and palladium tetrakis(triphenylphosphine) (0.668 g, 0.578 mmol) was pumped and backfilled with nitrogen 3 times. N,N-dimethylacetamide (30 mL) was added. The mixture was again pumped and backfilled with nitrogen 3 times. After heating to 110° C. for 15 h, the mixture was diluted with ethyl acetate (300 mL), washed with water (50 mL), brine (50 mL) and dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5-30% ethyl acetate in hexanes, gave 3-chloro-5-(3-methoxyphenyl)isonicotinonitrile as white solid (1.20 g, 43% yield). MS (ES+) m/z: 245 (M+H); LC retention time: 3.13 min (analytical HPLC Method A).

Provenance & Evidence