Ammonia → 4-(4-Nitrophenyl)piperidine-2,6-dione

Temperatur

10 °C

Alternatively, the title compound can be obtained in the following manner: A solution of 500 mg (1.97 mmol) of 3-(4-nitro-phenyl)-pentanedioic acid (as prepared in the previous step) in 50 mL dioxane was cooled to 10° C. and treated with 229 μL (2.96 mmol) of methyl chloroformate and 936 μL (6.71 mmol) of triethylamine for 7.2 h. A solution of 0.5 M ammonia in dioxane (15.8 mL, 7.90 mmol) was added at 10° C. and the mixture stirred at RT for 72 h. The mixture was filtered through Celite, the filter cake washed with EtOAc, and the solvents were evaporated in vacuo. The residue was treated with solid 1.30 g (15.8 mmol) of NaOAc and acetic anhydride (4 mL) and heated to 100° C. for 1 h. The mixture was cooled to RT and concentrated to half the original volume. The residue was taken up in EtOAc (100 mL), washed with saturated aqueous NaHCO3 (1×75 mL), brine (1×75 mL), and water (1×75 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 50-60% EtOAc-hexane afforded 197 mg (43%) of the title compound as an off-white solid (see spectrum above).

1. filtrationThe mixture was filtered through Celite
2. washthe filter cake washed with EtOAc
3. customthe solvents were evaporated in vacuo
4. temperatureheated to 100° C. for 1 h
5. temperatureThe mixture was cooled to RT
6. concentrationconcentrated to half the original volume
7. washwashed with saturated aqueous NaHCO3 (1×75 mL), brine (1×75 mL), and water (1×75 mL)
8. dry with materialThe organic layer was dried (MgSO4)
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-10344a247c714bf683a6b1b3034ae4e0

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08759347B2