Citric Acid → HCID 90060375, compound

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).

1. extractionThe mixture was extracted with ethyl acetate
2. extractionThe organic extract
3. washwas washed with a saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe resulting residue was dissolved in acetonitrile (5.0 mL)
7. additionan aqueous solution (2.0 mL) of 0.5 M citric acid was added
8. stirringThe mixture was stirred at 60° C. for 2 hours
9. additionWater was added to the reaction mixture, which
10. extractionwas followed by extraction with ethyl acetate
11. extractionThe organic extract
12. dry with materialwas dried over magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. dissolutionThe resulting residue was dissolved in acetonitrile (4.5 mL)
15. stirringThe mixture was stirred at room temperature for 2 hours
16. extractionwas followed by extraction with ethyl acetate
17. extractionThe organic extract
18. washwas washed with an aqueous solution of 10% sodium thiosulfate
19. dry with materiala saturated brine, dried over anhydrous magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. dissolutionThe resulting residue was dissolved in formic acid (3.0 mL)
22. stirringthe solution was stirred at room temperature for 5 hours
23. concentrationThe reaction mixture was concentrated
24. customthe resulting residue was purified by preparative HPLC

ORD record

ord-f1fec414786d4330b0f16455cd4769fe

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266853B2