反应详情

To a solution of 1-tert-butoxycarbonyl-4-(2-hydroxyethyl)piperazine (7.40 g, 32.13 mmol) in THF (100 mL), while stirring in an ice-bath, triethylamine (4.36 g, 43.09 mmol), 4-dimethylaminopyridine (200 mg, 1.64 mmol), and methanesulfonyl chloride (7.40 g, 38.76 mmol) were sequentially added. The temperature of the mixture was allowed to room temperature, and the mixture was stirred for 50 minutes. The reaction mixture was filtrated, and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (200 mL), and, at room temperature, 5,6-difluoro-2-mercaptobenzimidazole (5.00 g, 26.86 mmol), potassium carbonate (8.64 g, 62.51 mmol), and 18-crown-6 (500 mg, 1.92 mmol) were sequentially added to the solution, followed by stirring for 90 minutes at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1). The product was crystallized from acetone-ether-hexane, to thereby yield 1-tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine (7.26 g, yield 68%) as colorless crystals.

1. customwas allowed to room temperature
2. filtrationThe reaction mixture was filtrated
3. concentrationthe filtrate was concentrated under reduced pressure
4. dissolutionThe residue was dissolved in DMF (200 mL)
5. stirringby stirring for 90 minutes at 80° C
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. customthe residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1)
8. customThe product was crystallized from acetone-ether-hexane