Pyridine → HCID 23093485, compound

Participants

Reaction Steps

To a solution of bis(trichloromethyl)carbonate (0.53 g) in tetrahydrofuran (20 mL) was added dropwise a solution of pyridine (0.44 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 5 minutes under ice-cooling, and 3-methoxypropyl 2-(methylamino)ethyl carbonate hydrochloride (0.82 g) obtained in Reference Synthetic Example 49 was added thereto. A solution of triethylamine (0.75 mL) in tetrahydrofuran (1 mL) was added dropwise, and stirred at room temperature for 1 hr. The reaction solution was concentrated under reduced pressure, and to the residue was added water (50 mL), and then extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with 0.2 N hydrochloric acid (20 mL) and saturated brine (50 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (20 mL). To the solution were added (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole (1.11 g), triethylamine (0.63 mL) and 4-dimethylaminopyridine (0.037 g), and stirred at 60° C. for 6 hrs, and further at room temperature for 6 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (50 mL), and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was purified with basic silica gel column chromatography (eluted with ethyl acetate:hexane=3:7, then ethyl acetate:hexane=7:3). The purified material was crystallized from diethyl ether to give title compound as colorless solid (0.70 g).

Provenance & Evidence