Dimethylacetamide → 5-(Difluoromethoxy)-3-methylpicolinonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-5-(difluoromethoxy)-3-methylpyridine (12.4 g, 64.1 mmol), zinc cyanide (4.07 mL, 64.1 mmol), 1,1′-bis(diphenylphosphino)ferrocene (2.5 g, 4.51 mmol) and tris(dibenzylideneacetone)dipalladium(0) (2.1 g, 2.93 mmol) in DMA (50 mL) was heated to 110° C. under N2 for 18 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase obtained was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-70% EtOAc/hex to give 5-(difluoromethoxy)-3-methylpicolinonitrile (5.88 g, 31.9 mmol, 49.8% yield). MS m/z: 185.0 [M+H].

Provenance & Evidence