3-Hydroxybenzyl alcohol → (3-((5-(Trifluoromethyl)pyridin-2-yl)oxy)phenyl)methanol

Participants

Reaction Conditions

Reaction Steps

3-Hydroxymethyl-phenol (5.00 g, 40.3 mmol, from Lancaster Synthesis), 2-chloro-5-trifluoromethyl-pyridine (7.31 g, 40.3 mmol, from TCI America) and potassium carbonate (6.96 g, 50.3 mmol) were suspended in dimethylformamide (80 mL) and heated to 95° C. After stirring for 16 h, the solvent was distilled off in vacuo at 65° C., and a residue was partitioned between water and heptane/ethyl acetate (1:1). The organic layer was separated and the aqueous was extracted again with heptane/ethyl acetate (1:1). The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by silica gel chromatography (10-60%, EtOAc:heptane) to afford the desired product (5.70 g, 53% yield) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.73 (s, 2H) 7.02 (dt, J=8.66, 0.57 Hz, 1H) 7.04-7.11 (m, J=8.06, 2.40, 0.50, 0.50 Hz, 1H) 7.15-7.19 (m, 1H) 7.25 (ddd, J=8.39, 1.60, 0.80 Hz, 1H) 7.42 (t, J=7.87 Hz, 1H) 7.90 (ddd, J=8.67, 2.55, 0.50 Hz, 1H) 8.43 (td, J=1.68, 0.84 Hz, 1H).

Provenance & Evidence