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

Temperature

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 record

ord-43850bb740204deaa8c311ebf67a12d0

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296726B2