Diphenyl sulfide → HCID 68433593, compound

Temperature

0 °C

To a solution of 2-{5-[(E)-1-[3-chloro-4-(methylsulfanyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-4-iodo-1H-imidazol-2-yl}pyridine (0.340 g) in a mixed solvent of tetrahydrofuran (3 mL), methanol (3 mL) and water (3 mL) was added Oxone (registered trade mark) (777 mg) under ice-cooling, and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To a solution of the residue in a mixed solvent of acetonitrile (10 mL) and water (5 mL) was added sodium percarbonate (198 mg) under ice-cooling. The reaction solution was warmed to room temperature, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-100:0, volume ratio) to give a colorless oil. To a solution of the obtained oil in methanol (5 mL) were added 10% palladium carbon (30 mg), diphenylsulfide (0.7 μL) and triethylamine (0.29 mL). The reaction solution was purged with hydrogen, and stirred at room temperature for 16 hr. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-100:0, volume ratio) and recrystallized from hexane-ethyl acetate to give the title compound (0.047 g, yield 17%) as colorless crystals. melting point 106-109° C. MS: 446 (MH+).

1. temperaturecooling
2. extractionthe mixture was extracted with ethyl acetate
3. washThe extract was washed successively with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. additionTo a solution of the residue in a mixed solvent of acetonitrile (10 mL) and water (5 mL) was added sodium percarbonate (198 mg) under ice-
7. temperaturecooling
8. temperatureThe reaction solution was warmed to room temperature
9. stirringthe mixture was stirred at room temperature for 2 hr
10. additionA saturated aqueous ammonium chloride solution was added to the reaction mixture
11. extractionthe mixture was extracted with ethyl acetate
12. washThe extract was washed successively with water and saturated brine
13. dry with materialdried over anhydrous sodium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-100:0, volume ratio)
16. customto give a colorless oil
17. customThe reaction solution was purged with hydrogen
18. stirringstirred at room temperature for 16 hr
19. filtrationThe reaction mixture was filtered
20. concentrationthe filtrate was concentrated under reduced pressure
21. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-100:0, volume ratio)
22. customrecrystallized from hexane-ethyl acetate

ORD record

ord-f8add5edd884487382c1a74130815c23

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318746B2