Nitrogen → 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-(methylthio)-1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile

Participants

Reaction Steps

To a magnetically stirred mixture of 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4,5-dihydro-1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile (100 mg, 0.199 mmol) in dry THF (1990 μL) was added sodium hydride (17.51 mg, 0.438 mmol) in a 10 mL vial under N2 atmosphere. The reaction mixture was stirred at 0° C. for 15 min at which point methyl iodide (12.44 μL, 0.199 mmol) was added via microsyringe. The reaction was allowed to continue stifling at 0° C. for 1 hour. At this point the reaction was quenched with water and allowed to stir, then removed from the ice bath and extracted with CH2Cl2 (3×). The combined organic layers were dried by passing through a phase separator and volatiles were removed under a gentle stream of N2. The resulting residue was loaded onto a pad of celite and purified (SiO2, 10-35% Ethyl Acetate/Hexanes over 8 min, 35% for 4 min) to give the title compound as an off white foamy solid (82 mg, 76%).

Provenance & Evidence