Citric Acid → HCID 90060375, compound

Participants

Reaction Steps

1-tert-Butyl (2S,3S)-2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-[(E)-8-(2-heptyl-[1,3]dioxolan-2-yl)-oct-1-enyl]-2-hydroxy-succinate (787 mg, 1.05 mmol) and (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propyl acetate hydrochloride (375 mg, 1.26 mmol) were dissolved in DMF (18 mL), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (439 mg, 1.16 mmol) and N,N-diisopropylethylamine (814 μL, 4.73 mmol) were added. The mixture was stirred at room temperature for 2 hours. To the reaction mixture was then added an aqueous solution of 0.5 M potassium hydrogen sulfate. The mixture was extracted with ethyl acetate. The organic extract was washed with a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (5.0 mL), and an aqueous solution (2.0 mL) of 0.5 M citric acid was added. The mixture was stirred at 60° C. for 2 hours. Water was added to the reaction mixture, which was followed by extraction with ethyl acetate. The organic extract was dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (4.5 mL) and water (1.0 mL), and 4-acetamide-2,2,6,6-tetramethylpiperidine-1-oxyl (16.8 mg, 78.8 μmol) and diacetoxyiodobenzene (372 mg, 1.16 mmol) were added. The mixture was stirred at room temperature for 2 hours. An aqueous solution of citric acid was added to the reaction mixture, which was followed by extraction with ethyl acetate. The organic extract was washed with an aqueous solution of 10% sodium thiosulfate and a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in formic acid (3.0 mL) and the solution was stirred at room temperature for 5 hours. The reaction mixture was concentrated and the resulting residue was purified by preparative HPLC to obtain the title compound (12.3 mg).

Provenance & Evidence