Pyridine → HCID 23093491, compound

To a solution of bis(trichloromethyl)carbonate (0.59 g) in tetrahydrofuran (20 mL) was added dropwise a solution of pyridine (0.49 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 10 minutes under ice-cooling, and 2-methoxyethyl 2-(methylamino)ethyl carbonate hydrochlride (1.07 g) obtained in Reference Synthetic Example 18 was added. A solution of triethylamine (0.84 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 extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with 0.2 N hydrocloric 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 (1.85 g), triethylamine (1.05 mL) and 4-dimethylaminopyridine (0.061 g), and stirred at 60° C. for 6 hrs, and then at room temperature for 8 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 saline (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). The purified material was crystallized from ethyl acetate-diethyl ether, and further recrystallized from ethyl acetate-diisopropyl ether to give title compound as colorless solid (1.39 g).

1. temperaturecooling
2. temperaturecooling

ORD record

ord-6a51a86f074543288f5589b765eaea6f

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2