1,1,1-Trifluoro-2-iodoethane → 6-(3,3,3-Trifluoropropyl)pyridine-3-carbonitrile

Participants

Reaction Steps

To a solution of 6-methyl-nicotinonitrile (118 mg, 1.0 mmol) in anhydrous THF (20 mL) at −78 C under nitrogen was added lithium diisopropylamine (2M solution in THF/heptane/ethylbenzene, 550 μL, 1.1 mmol) drop-wise. The resulting solution was allowed to warm to room temperature for 5 min and then cooled back to −78 C. 1,1,1-Trifluoro-2-iodo-ethane (524 mg, 2.5 mmol) was then added to the solution drop-wise and the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 2 h. The reaction mixture was cooled at 0 C and quenched with water; the resulting solution was extracted with EtOAc (3×25 mL). Combined organics were washed with brine (25 mL), dried over magnesium sulfate and purified by silica chromatography (25% EtOAc in heptane) to afford the title compound as a pale yellow oil (191 mg, 95%). Method C HPLC-MS: MH+ requires m/z=201. Found: m/z=201, Rt=1.22 min (86%).

Provenance & Evidence