Benzyl Alcohol → 4-((6-(benzyloxy)-3-fluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

Benzyl alcohol (352 mg, 3.26 mmol) was dissolved in anhydrous DMF (2 ml) and placed under argon. This was then treated with a 60% dispersion in oil of SODIUM HYDRIDE (78.7 mg, 3.26 mmol). This resultant suspension was then stirred at room temperature for 15 min. At this time it was treated with a solution of 4-((3,6-difluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrile (275 mg, 1.09 mmol) dissolved in anhydrous DMF (2 ml). Once the addition was complete the reaction was stirred at 90° C. for 5 hours. The reaction was allowed to cool to room temperature. It was then poured into brine (20 ml). This was extracted with EtOAc (3×15 ml). The combined extracts were washed with H2O (3×10 ml) followed by brine (1×10 ml). The organic layer was dried (Na2SO4), filtered, and the solvent removed in vacuo to give the crude material which was purified using the ISCO and a 12 g SiO2 column. Eluted using 100 hexanes to 30 EtOAc/70 hexanes over 20 min. 245 mg (66% yield) of the desired product was obtained as a viscous liquid. LCMS (m/z): 342.1 [M+H]+; retention time=1.017 min.

Provenance & Evidence