Thionyl Chloride → 5-Chloropyridine-2-carbonyl chloride

N,N-Dimethylformamide (one drop) and thionyl chloride (1 mL) were added to a suspension of 5-chloropyridinecarboxylic acid (55.2 mg) in toluene (5 mL). The mixture was heated under reflux for one hour. The reaction solution was cooled to room temperature and then the solvent was evaporated under reduced pressure to obtain 5-chloropyridinecarboxylic acid chloride. A solution of 5-chloropyridinecarboxylic acid chloride in THF (5 mL) and pyridine (115 μL) were sequentially added to a solution of the compound of Preparation Example 2-(2) (111 mg) in THF (10 mL) under ice-cooling. The mixture was warmed to room temperature and stirred for 30 minutes. After confirming completion of the reaction, a saturated sodium bicarbonate solution was added to the mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to obtain an amide compound of a synthetic intermediate. The resulting amide was dissolved in dichloromethane (10 mL). Trifluoroacetic acid (2 mL) was added and the mixture was stirred at room temperature for three hours. The reaction solution was diluted with diethyl ether. Then, the reaction mixture was neutralized with a sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The crude product was purified by NH-silica gel column chromatography to obtain the title compound (115 mg; >99% ee).