反应详情

Triethylamine (1.04 g, 10.3 mmol) and 4-dimethyl aminopyridine (104 mg, 0.854 mmol) were added to a solution of 1-tert-butoxycarbonyl-4-(2-hydroxyethyl)piperazine (2.00 g, 8.54 mmol) in tetrahydrofuran (THF) (30 mL) in an ice bath, and the solutes were dissolved by stirring. Methanesulfonyl chloride (1.37 g, 12.0 mmol) was added dropwise to the solution in the ice bath over a period of 5 minutes with stirring, and the mixture was stirred for 1 hour in an ice bath. After the completion of the reaction, the insoluble content was removed by filtration, and the thus removed insoluble content was washed with THF (10 mL×2). The filtrate and the washing solution were combined and concentrated under reduced pressure to such degree that substantially no solvent was left. The concentrate was diluted with DMF (20 mL). To the solution was added 2-mercaptobenzimidazole (1.41 g, 9.39 mmol), potassium carbonate (1.77 g, 12.8 mmol), and 18-crown-6 (226 mg, 0.854 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and the resulting concentrate was diluted and separated with ethyl acetate (10 mL) and water (50 mL). The aqueous layer was further extracted with ethyl acetate (10 mL×2), and the extract was combined with the organic layer, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. It was then purified by silica gel column chromatography (chloroform/methanol saturated with ammonia=40/1) to give 1-[2-(benzimidazol-2-ylthio)ethyl]-4-tert-butoxycarbonyl piperazine 2.02 g (64%) as colorless powdery crystals.

1. dissolutionthe solutes were dissolved
2. stirringwith stirring
3. stirringthe mixture was stirred for 1 hour in an ice bath
4. customAfter the completion of the reaction
5. customthe insoluble content was removed by filtration
6. washthe thus removed insoluble content was washed with THF (10 mL×2)
7. concentrationconcentrated under reduced pressure to such degree that substantially no solvent
8. waitwas left
9. additionThe concentrate was diluted with DMF (20 mL)
10. stirringthe mixture was stirred at 80° C. for 3 hours
11. concentrationThe reaction solution was concentrated under reduced pressure
12. concentrationthe resulting concentrate
13. additionwas diluted
14. customseparated with ethyl acetate (10 mL) and water (50 mL)
15. extractionThe aqueous layer was further extracted with ethyl acetate (10 mL×2)
16. washwashed with saturated aqueous sodium chloride
17. dry with materialdried over anhydrous sodium sulfate
18. customIt was then purified by silica gel column chromatography (chloroform/methanol saturated with ammonia=40/1)