Dimethyl acetylenedicarboxylate → 5-Bromo-2-fluoropyridine-3-carbonitrile

Participants

Reaction Steps

To a solution of 5-Bromo-2-fluoro-pyridine-3-carbaldehyde oxime (3) (19.0 g, 86.8 mmol) in MeCN (400 mL) was added dimethylacetylene dicarboxylate (25.0 g, 176 mmol) and TEA (24.1 mL, 173 mmol) dropwise. The reaction mixture was stirred at rt for 4 hours. The solvent was evaporated in vacuo and the residue diluted with CHCl3 (300 mL) and H2O (300 mL). The layers were separated and the organic phase washed with saturated brine solution (200 mL), then dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (100-200 mesh silica gel, 10% EtOAc-pet ether) to provide the title compound as a white solid (12.0 g, 69%); Rf: 0.7 (20% EtOAc-pet ether).

Provenance & Evidence