Hexamethylphosphoramide → 2-(4-Bromo-2-methylphenyl)-3-pyridin-3-ylpropanenitrile

Participants

Reaction Conditions

Reaction Steps

To a solution (4-bromo-2-methylphenyl)acetonitrile (III.1; 1 eq.) in THF (0.18M) and hexamethylphosphoramide (HMPA; 3.3 eq.) at −78° C. was added lithium hexamethyldisilazide (LiHMDS; 1.9 eq.). The reaction mixture was stirred 30 min at −78° C. To the resulting solution was cannulated a suspension of 3-(bromomethyl)pyridine hydrobromide salt (0.8 eq.) in THF (0.1M). The final mixture was allowed to warm slowly to 0° C., stirred 2 h, warm to room temperature then stirred for an extra 2 h. The resulting mixture was poured in saturated aqueous NaHCO3 and finally extracted with EtOAc. The organic extract was washed with water, brine, dried over Na2SO4 filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 60% in 30 min) afforded the desired compound as a colorless oil.

Provenance & Evidence