Ammonium Chloride → HCID 67282946, compound

Sodium borohydride (2.15 g) was added to a methanol-THF (20 ml-100 ml) solution of the compound 321-1 (17.4 g), while the solution was stirred under cooling on ice. The obtained mixture was stirred at room temperature for 1 hour. A saturated ammonium chloride aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The obtained residue was dissolved in dichloromethane (100 ml). Triethylamine (19.8 ml) and methanesulfonyl chloride (8.05 ml) were added to the solution, while the solution was stirred under cooling on ice. The obtained mixture was stirred at room temperature for 14 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile (100 ml). Sodium iodide (2.83 g) and sodium cyanide (6.95 g) were added to the solution, and the obtained mixture was stirred at 80° C. for 3 hours. Thereafter, sodium cyanide (9.27 g) and dimethyl sulfoxide (30 ml) were added to the reaction solution, and the obtained mixture was stirred at 100° C. for 5 hours. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and the mixture was then extracted with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride aqueous solution, then dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=1:0 to 1:1), so as to obtain the title compound (11.5 g).

1. temperatureunder cooling on ice
2. stirringThe obtained mixture was stirred at room temperature for 1 hour
3. extractionthe mixture was extracted with ethyl acetate
4. dry with materialThe obtained organic layer was dried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe obtained residue was dissolved in dichloromethane (100 ml)
7. additionTriethylamine (19.8 ml) and methanesulfonyl chloride (8.05 ml) were added to the solution, while the solution
8. stirringwas stirred
9. temperatureunder cooling on ice
10. stirringThe obtained mixture was stirred at room temperature for 14 hours
11. additionWater was added to the reaction solution
12. extractionthe mixture was extracted with ethyl acetate
13. dry with materialThe obtained organic layer was dried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. dissolutionThe obtained residue was dissolved in acetonitrile (100 ml)
16. additionSodium iodide (2.83 g) and sodium cyanide (6.95 g) were added to the solution
17. stirringthe obtained mixture was stirred at 80° C. for 3 hours
18. additionThereafter, sodium cyanide (9.27 g) and dimethyl sulfoxide (30 ml) were added to the reaction solution
19. stirringthe obtained mixture was stirred at 100° C. for 5 hours
20. concentrationThe reaction solution was concentrated under reduced pressure
21. additionWater was added to the residue
22. extractionthe mixture was then extracted with ethyl acetate
23. washThe obtained organic layer was washed with a saturated sodium chloride aqueous solution
24. dry with materialdried over magnesium sulfate
25. concentrationconcentrated under reduced pressure
26. customThe obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=1:0 to 1:1)

ORD record

ord-e7dd30fa449e46ba890941c266257070

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268848B2