Potassium Carbonate → HCID 53482821, compound

Participants

Reaction Steps

To a solution of (3R,4R)-benzyl 3-(((S)-2-acetoxy-N—((R)-1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (1.78 g, 2.53 mmol) in degassed EtOAc (25 mL, 0.1 M solution) was added Pd/C (178 mg, 10 wt %) under anhydrous N2 atmosphere. After flushed with hydrogen gas, the reaction mixture equipped with a hydrogen gas balloon was stirred at room temperature for overnight. The reaction mixture was filtered through Celite® pad that was washed with EtOAc. The volatile organic filtrate was removed in vacuo to give the crude amine (LC/MS (uplc): MH+ 572.4, 1.11 min). Then, the crude product was dissolved in MeOH (168 mL, 0.015 M solution) followed by addition of anhydrous potassium carbonate (3.5 g, 25 mmol). The reaction was then stirred for 15 min at room temperature. After white precipitate was removed by filtration, the organic filtrate was concentrated in vacuo. The crude product was purified by preparative reverse phase HPLC. The combined fractions of the product were neutralized with saturated NaHCO3 solution, which was then extracted with EtOAc (200 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The dried product was then dissolved in acetonitrile and water (1:1 ratio) and lyophilized for 48 h. The white powdery (S)—N—((R)-1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)-N-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)-2-hydroxypropanamide was obtained in 65.5% yield (876 mg, over 3 steps) as a free amine 1H NMR (CD3Cl, 400 MHz): 7.82 (1H, m), 7.52 (2H, m), 7.34-7.25 (3H, m), 7.16 (1H, m), 7.07 (1H, m), 6.09 (1H, s), 5.44 (2H, s), 4.61 (2H, m), 4.39 (1H, m), 3.78 (1H, m), 3.60 (1H, m), 2.92 (1H, m), 2.56 (1H, m), 2.16 (2H, m), 1.44 (3H, m), 1.22 (1H, m), 0.99 (9H, s), 0.42 (1H, m). LC/MS (uplc): MH+ 530.3, 1.05 min.

Provenance & Evidence