Oxalyl chloride → 3-Pyridinecarbonyl chloride, hydrochloride (1:1)

Participants

Reaction Steps

To a solution of nicotinic acid hydrochloride (0.5 g, 3.1 mmol) in CH2Cl2 (200 mL) at room temperature was added oxalyl chloride (0.42 mL, 4.8 mmol) and three drops of DMF. The reaction mixture was stirred at room temperature for 1 h and then concentrated using a rotary evaporator. The resulting residue was re-dissolved in toluene (50 ml), and then again concentrated using a rotary evaporator to afford nicotinic acid chloride hydrochloride (0.5 g, 90%). To a solution of 2′-hydroxyacetophenone (0.38 g, 2.8 mmol) in THF (50 mL) at room temperature was added nicotinic acid chloride hydrochloride (0.5 g, 2.8 mmol) and triethylamine (1.2 mL, 8.6 mmol). The reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with water (50 mL), extracted with CH2Cl2 (3×100 mL), concentrated using a rotary evaporator. The residue was purified by column chromatography (hexane:ethyl acetate 2:1) to provide the corresponding ester (0.42 g, 62%). A solution of the above ester (0.42 g, 1.73 mmol) in THF (50 mL) was mixed with t-BuOK (0.25 g, 2.25 mmol) and was stirred at room temperature for 16 hours. The reaction was quenched with water (50 mL) and the aqueous was acidified with HCl (0.5 N) to pH=6. The reaction mixture was extract with CH2Cl2 (3×100 mL), concentrated using a rotary evaporator, trituration in hexanes to afford a solid. This solid was collected by filtration and washed with hexanes to provide the diketone (0.3 g, 71%). A solution of the above diketone (0.3 g, 1.25 mmol) in HOAc (50 mL) and HCl (conc., 1 mL) was stirred at reflux for 2 hours. The solvent was removed using a rotary evaporator. The residue was purified by column (hexane:ethyl acetate:MeOH 3:3:1) to provide 2-(pyridin-3-yl)-4H-chromen-4-one as a light yellow solid (0.202 g, 73%); MS (ES) m/z: 224.90 (M+1), 223.92 (M); MP 122.8-124.0° C.

Provenance & Evidence