Pyridine → HCID 66894309, compound

To a solution of bis(trichloromethyl)carbonate (0.50 g) in tetrahydrofuran (30 mL) was added dropwise a solution of pyridine (0.40 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 1 hr under ice-cooling, and (S)-2-pyrrolidinylmethyl acetate hydrochloride (0.90 g) obtained in Reference Synthetic Example 31 was added thereto. A solution of triethylamine (0.70 mL) in tetrahydrofuran (1 mL) was added dropwise, and stirred at room temperature for 2 hrs. The reaction solution was concentrated under reduced pressure. To the residue was added water (50 mL), and extracted with ethyl acetate (50 mL), and then, 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 (0.84 mL) and 4-dimethylaminopyridine (0.037 g), and stirred at 60° C. for 1 day, and then at room temperature for 2 days. 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=1:1, then ethyl acetate), and further with silica gel column chromatography (eluted with ethyl acetate:hexane=3:1, then ethyl acetate, then acetone:ethyl acetate=1:4, then 2:3) to give title compound as pale yellow amorphous solid (0.80 g).

1. temperaturecooling
2. temperaturecooling

ORD record

ord-7060bbe24cb146318a920f773242f317

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2