反应详情

温度

120 °C

In a round bottomed flask equipped with a magnetic stirrer, (R)-2-amino-3-methyl-N-(2,2,2-trifluoroethyl)butanamide hydrochloride (1-3b) (20 g, 85 mmol), 3,5-Dibromopyridine (30.3 g, 128 mmol), Potassium carbonate (35.3 g, 256 mmol) were suspended in DMSO (71 ml, 1.2M) and reaction mixture was purged with nitrogen for 20 minutes, then Copper(I) Iodide (0.974 g, 5.1 mmol) was added and the reaction mixture was slowly heated to 120° C. overnight. The cooled reaction mixture was then partitioned between Isopropanol (IPA):Chloroform (1:3) and Water, the aqueous layer was extracted with three times with IPA:Chloroform mixture. The combined organic layers were extracted with 1M solution of EDTA disodium salt, dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude sample. Purification on a silica gel column using a gradient 0-40% ethyl acetate:hexane gave an orange solid which was taken up in ethyl acetate and concentrated to an oil, hexane was added dropwise while stirring, a white solid crystallized which was filtered, washed with hexane and dried under vacuum to give 14 g, (46.4%) the title compound, I-3, as a white solid.

1. customIn a round bottomed flask equipped with a magnetic stirrer
2. customreaction mixture
3. customwas purged with nitrogen for 20 minutes
4. customThe cooled reaction mixture
5. customwas then partitioned between Isopropanol (IPA)
6. extractionChloroform (1:3) and Water, the aqueous layer was extracted with three times with IPA
7. extractionThe combined organic layers were extracted with 1M solution of EDTA disodium salt
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude sample
12. customPurification on a silica gel column
13. customhexane gave an orange solid which
14. concentrationconcentrated to an oil, hexane
15. additionwas added dropwise
16. customa white solid crystallized which
17. filtrationwas filtered
18. washwashed with hexane
19. customdried under vacuum