1-Methyl-3-phenyl-1H-1,2,4-triazole → (2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-methyl-3-phenyl-1H-1,2,4-triazole (1.56 g, 9.83 mmol) in THF (50 mL) cooled to −78° C. was added 1.6 M n-butyl lithium (6.76 ml, 10.8 mmol) drop-wise and stirred for 30 min. Next a solution of Intermediate 416.2 (2.46 g, 11.8 mmol) in THF (15 mL) was added drop-wise and stirred for 5 min before allowing the mixture to warm to 23° C. The reaction mixture was quenched with aqueous NH4Cl and extracted with EtOAc (3×50 mL). The organic layer was washed with H2O, brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient) to afford 3.6 g of Intermediate 416.3. 1H NMR (400 MHz, CDCl3) δ ppm 1.59 (s, 3H) 3.62 (s, 3H) 3.66-3.78 (m, 2H) 3.91-4.04 (m, 2H) 6.22 (s, 1H) 6.94-7.07 (m, 1H) 7.32-7.49 (m, 5H) 7.70 (dd, J=7.25, 2.42 Hz, 1H) 7.97-8.05 (m, 2H).

Provenance & Evidence