Hydrochloric Acid → HCID 66731665, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (3.5 g, 20.40 mmol), 2-chloro-4-fluorophenylboronic acid (3.91 g, 22.44 mmol), potassium carbonate (2.114 g, 15.30 mmol) and PdCl2 (dppf) (0.443 g, 0.61 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a dark-brown solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The MTBE layer was treated with hydrogen chloride (4 M in dioxane, 5.10 mL, 20.40 mmol) and stirred for 1 h at room temperature. The precipitate was collected by filtration. Methyl 2-(2-chloro-4-fluorophenyl)isonicotinate (2.350 g, 38.1%) was obtained as a light yellow solid. 1H NMR (400 MHz, cdcl3) δ 4.13 (s, 3H), 7.24-7.33 (m, 1H), 7.36 (d, 1H), 7.82-8.03 (m, 1H), 8.34 (s, br., 1H), 8.56 (s, br., 1H), 9.08 (s, br., 1H). MS m/z 266 (M+H)+

Provenance & Evidence