Acetic Anhydride → 3,5-Dioxohexanoic acid

4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenoxy)butanoic acid (39, 1.47 g, 3.2 mmol), 2-amino-2-methyl-1-(4-methylpiperazin-1-yl)propan-1-one (1.07 g, 2 HCl salt, 4.1 mmol), HATU (1.45 g, 3.8 mmol), and DIPEA (2.2 mL, 13 mmol) were combined in CH3CN (32 mL) and stirred overnight at room temperature. To the reaction were added DMAP (39 mg, 0.32 mmol), DIPEA (3.3 mL, 19 mmol), and acetic anhydride (1.5 mL, 16 mmol). The reaction was stirred for 1 hour, then quenched with saturated aqueous NaHCO3, stirred for 1 hour, and extracted twice with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (gradient 2-10% MeOH/CH2Cl2) to yield 2.27 g (94% yield) of triacetate as a yellow foam.

1. stirringThe reaction was stirred for 1 hour
2. customquenched with saturated aqueous NaHCO3
3. stirringstirred for 1 hour
4. extractionextracted twice with EtOAc
5. washThe combined organic phases were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customThe residue was purified by silica gel chromatography (gradient 2-10% MeOH/CH2Cl2)

ORD record

ord-2fc2e7bd31e3404e8b135314db8731ca

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200025B2