Hydrochloric Acid → HCID 66732390, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (4.5 g, 26.23 mmol), 4-fluorophenylboronic acid (4.51 g, 32.26 mmol), potassium carbonate (2.247 g, 16.26 mmol) and PdCl2 (dppf) (0.380 g, 0.52 mmol) were mixed in methanol (30 mL) in two 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. To the residue was added HCl (1.25 M in methanol, 100 mL). The mixture was stirred at 45° C. for 4 h, then concentrated. Satd NaHCO3 (100 mL) was added under ice cooling and extracted with DCM (3×100 mL) The combined organic phases were washed with brine, passed through a phase separator and evaporated to yield a brown solid. The crude was dissolved in MTBE (180 mL) and some solids were filtered off. Cooled with ice-water, hydrogen chloride (4 M in dioxane, 10 mL, 40 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at 0° C. for 10 min. The solid was collected by filtration and washed with MTBE to yield methyl 2-(4-fluorophenyl)isonicotinate hydrochloride (6.4 g, 91%) as a beige solid. 1H NMR (400 MHz, cd3od) d 4.07 (s, 3H), 7.37-7.51 (m, 2H), 8.02-8.13 (m, 2H), 8.37 (dd, 1H), 8.71 (d, 1H), 8.97 (dd, 1H). MS m/z 232 (M+H)+

Provenance & Evidence