Nitrogen → 5-Chloro-2-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)pyridine

Participants

Reaction Conditions

Reaction Steps

To a magnetically stirred mixture of 6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-ol (400 mg, 1.337 mmol) and 5-chloro-2-fluoropyridine (805 μL, 8.02 mmol) in dry DMSO (13.4 mL) was added cesium carbonate (871 mg, 2.67 mmol) in a 20 mL vial under N2 atmosphere. The reaction mixture was stirred at 75° C. for 2 h, then rt for 12 h. The reaction as heated to 75° C. for an additional 30 min then cooled to rt, diluted with Et2O and poured into a separatory funnel containing water. The aqueous layer was extracted with Et2O (3×) and then the combined organic layers were washed with 1:1 brine:H2O (3×) then once with brine and dried by passing through a phase separator. Volatiles were removed by rotary evaporation and the crude residue was loaded onto a pad of Celite® and purified by flash chromatography (SiO2, 10% EtOAc/Hexanes for 5 min then ramp to 25% over 8 min-paused gradient at 25%) to yield the title compound as a colorless oil (91 mg, 16.6%): 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J=2.4 Hz, 1H), 8.14-8.07 (m, 1H), 7.72 (dd, J=8.7, 2.7 Hz, 1H), 7.57 (dd, J=8.6, 2.5 Hz, 1H), 7.52 (dd, J=8.6, 0.6 Hz, 1H), 7.40 (dd, J=14.7, 8.2 Hz, 1H), 7.00 (dd, J=8.6, 0.4 Hz, 1H), 6.88-6.82 (m, 1H), 6.76 (ddd, J=9.9, 9.0, 2.5 Hz, 1H), 3.46 (d, J=5.1 Hz, 1H), 3.03-2.96 (m, 1H); 19F NMR (376 MHz, CDCl3) δ −106.83 (dd, J=257.5, 8.3 Hz, 1F), −107.38-−108.26 (m, 2F), −109.27 (q, J=8.4 Hz, 1F); ESIMS m/z 412 ([M+H]+).

Provenance & Evidence