Pyridine → HCID 23071196, compound

To a solution of bis(trichloromethyl)carbonate (0.582 g) in tetrahydrofuran (20 mL) was added dropwise a solution of pyridine (0.485 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 20 minutes under ice-cooling, and 2-(methylamino)ethyl tetrahydropyran-4-yl carbonate hydrochloride (1.43 g) obtained in Reference Synthetic Example 17 was added thereto. A solution of triethylamine (0.84 mL) in tetrahydrofuran (1 mL) was added dropwise, and stirred at room temperature for 3 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (30 mL), and then extracted with ethyl acetate (80 mL). The ethyl acetate layer was washed with saturated brine (20 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 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole (1.63 g), triethylamine (1.23 mL) and 4-dimethylaminopyridine (0.027 g), and stirred at 60° C. for 17.5 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (50 mL), and extracted with ethyl acetate (120 mL). The ethyl acetate layer was washed with saturated brine (30 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=1:2, then 1:1), and further purified with silica gel column chromatography (eluted with ethyl acetate:hexane=1:1, then 2:1). The purified material was crystallized from diethyl ether to give title compound as colorless solid (1.23 g).

1. temperaturecooling
2. temperaturecooling

ORD record

ord-728cb79db6064e38b65e78309a06fb52

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2