Thionyl Chloride → HCID 15479726, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-boronobenzoic acid (4.15 g, 25 mmol) and 3-bromopyridine (4.3 g, 27.5 mmol) in acetonitrile (60 mL) and water (60 mL), potassium carbonate (13.8 g, 100 mmol), bis(triphenylphosphine)palladium(II) chloride (1.75 g, 2.5 mmol) was added. The mixture was degassed and purged withed nitrogen. The mixture was stirred under reflux for 24 hours. Then the hot suspension was filtered and concentrated to half of the original volume and washed with dichloromethane. The aquatic phase was adjusted to pH=3 with hydrochloric acid (1 M) and filtrated, washed with water. The residue was dried in vacuum to obtain 4 g of white solid of 4-(pyridin-3-yl)benzoic acid. (Yield: 80%. LC-MS (ESI) m/z: 200 (M+1)+). Thionyl chloride (10 ml) was added to 4-(pyridin-3-yl)benzoic acid (4 g, 20 mmol) and the mixture was stirred at 70° C. overnight. The solvent was evaporated under reduced pressure and the residue was dried in vacuum. 4.5 g of crude 4-(pyridin-3-yl)benzoyl chloride was obtained. To a solution of methyl 3-amino-2-hydroxybenzoate (2.9 g, 17 mmol) and pyridine (4 g, 52 mmol) in toluene (50 ml) were added 4-(pyridin-3-yl)benzoyl chloride (4.5 g, 20.4 mmol) portion-wise at 0° C. and then stirred at 70° C. for 4 h. The resulting mixture was extracted with ethyl acetate (100 mL×4), the organic phase was washed with water and saturated sodium bicarbonate, dried with anhydrous sodium sulfate and evaporated under reduced pressure to obtain methyl 2-hydroxy-3-(4-(pyridine-3-yl)enzamido)benzoate as a yellow solid (5 g, yield 85%). LC-MS (ESI) m/z: 349 (M+1)+.

Provenance & Evidence