Triethylamine → HCID 51348929, compound

Participants

Reaction Steps

To a solution of (1R)-3-amino-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(2-hydroxyethyl)cyclopentanecarboxamide (from step F, 30 mg, 0.061 mmol) in THF (1 mL) was added carbonyl diimidazole (14.77 mg, 0.091 mmol) and triethylamine (0.021 mL, 0.152 mmol). The resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated and subjected preparative HPLC(Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA; wavelength: 220 nM) to yield the desired product as a diastereomer mixture. The diastereomer mixture was subjected to chiral preparative HPLC (Column: ChiralPak ASH, 250×3 cm, 5 μm; Flow rate: 120 mL/min; Mobile Phase: CO2/MeOH=80/20; Inj. Vol.=2.0 mL, Wavelength=220 nM; isomer 1, retention time=5.75 min; isomer 2, retention time=9.10 min) to yield the individual diasteromers (2 mg for each isomer, 3.85 μmol, 6.33% yield) as a solid.

Provenance & Evidence