反应详情

温度

70 °C

(S)—N-(pent-4-ynyl)-2-(2,2,2-trifluoroacetamido)butanamide (0.246 g, 0.93 mmol), 4-bromophenyl methyl sulfone (0.200 g, 0.85 mmol), triethylamine (5 ml), copper iodine (0.032 g, 0.17 mmol) and Pd(PPh3)2Cl2 (0.175 g, 0.25 mmol) were combined in anhydrous DMF (5 ml) and heated to 70° C. in a sealed tube overnight. The resulting mixture was then concentrated in vacuo and ethyl acetate (46 ml) was added to the remaining residue. The resulting mixture was washed with 1N HCl (2×23 ml), water (23 ml), brine (23 ml), dried (MgSO4) and concentrated in vacuo. The resulting residue was chromatographed eluting with ethyl acetate/heptanes (30:70) to yield a residue. The residue was dissolved in THF (0.5 ml)/MeOH (0.13 ml) and cooled to 0° C. 3N NaOH (0.10 ml, 0.30 mmol) was added, the resulting mixture was warmed to room temperature and stirred overnight. The resulting mixture was then diluted with water (0.25 ml) and concentrated in vacuo. The aqueous layer was extracted with methylene chloride (3×5 ml), dried (MgSO4) and concentrated in vacuo. The resulting residue was chromatographed eluting with methylene chloride/methanol (95:5) followed by elution with methylene chloride/methanol/ammonium hydroxide (95:5:0.4) to yield (S)-2-amino-N-(5-(4-(methylsulfonyl)phenyl)pent-4-ynyl)butanamide. ES-MS m/z 323 (MH+).

1. concentrationThe resulting mixture was then concentrated in vacuo and ethyl acetate (46 ml)
2. additionwas added to the remaining residue
3. washThe resulting mixture was washed with 1N HCl (2×23 ml), water (23 ml), brine (23 ml)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was chromatographed
7. washeluting with ethyl acetate/heptanes (30:70)
8. customto yield a residue
9. temperaturecooled to 0° C
10. temperaturethe resulting mixture was warmed to room temperature
11. concentrationconcentrated in vacuo
12. extractionThe aqueous layer was extracted with methylene chloride (3×5 ml)
13. dry with materialdried (MgSO4)
14. concentrationconcentrated in vacuo
15. customThe resulting residue was chromatographed
16. washeluting with methylene chloride/methanol (95:5)
17. washfollowed by elution with methylene chloride/methanol/ammonium hydroxide (95:5:0.4)