Hydrochloric Acid → Methyl 2-(4-tert-butylphenyl)isonicotinate hydrochloride

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (7 g, 40.80 mmol), 4-tert-butylphenylboronic acid (10 g, 56.17 mmol), potassium carbonate (3.5 g, 25.32 mmol) and PdCl2 (dppf) (0.9 g, 1.24 mmol) were mixed in methanol (30 mL) in two equal portions in 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. The solids were removed by filtration and the filtrate evaporated to yield a dark red slurry. DCM and brine were added and the phases separated. The water phase (pH 9) was extracted with DCM and the combined organic phases dried over MgSO4 and evaporated. The crude was dissolved in MTBE (180 mL) and the solids filtered off. Hydrogen chloride (4 M in dioxane, 10.20 mL, 40.80 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 1 h. The solid was collected by filtration and washed with MTBE. Methyl 2-(4-tert-butylphenyl)isonicotinate hydrochloride (9.6 g, 77%) was isolated as a dark brown solid. 1H NMR (400 MHz, dmso) δ 1.30 (s, 9H), 3.92 (s, 3H), 7.53 (d, 2H), 7.80 (dd, 1H), 8.04 (d, 2H), 8.29 (s, 1H), 8.85 (d, 1H), 9.86 (br, 1H). MS m/z 270 (M+H)+

Provenance & Evidence