Triethylamine → (S)-2-amino-N-(5-(4-(methylsulfonyl)phenyl)pent-4-ynyl)butanamide

Participants

Reaction Conditions

Reaction Steps

(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+).

Provenance & Evidence