Dimethylformamide → Methyl 5-cyano-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate

Participants

Reaction Conditions

Reaction Steps

To a solution of 627 mg (2.21 mmol) of methyl 5-chloro-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate (from Step B), 123 mg (0.22 mmol), 156 mg (1.33 mmol) of zinc cyanide, and 29 mg (0.44 mmol) of zinc dust in 5.0 ml of DMF was added 101 mg (0.11 mmol) of tris(dibenzylideneacetone)dipalladium(0). After stirring at 120° C. overnight, the mixture was filtered through a cake of Celite and washed with EtOAc. The filtrate was washed with brine (10 mL), H2O (3×10 mL), and brine (10 mL). The organic layer was dried over MgSO4 and concentrated. Chromatography on a Biotage 40M cartridge using 1:9 v/v EtOAc/hexanes as the eluant gave 498 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.59 (d, J=6.6, 3H), 3.97 (s, 3H), 5.93 (m, 1H), 8.54 (d, J=2.2, 1H), 8.96 (d, J=2.3, 1H).

Provenance & Evidence