Methylamine → 1-Methyl-4-(4-nitrophenyl)piperidine-2,6-dione

HRID 1008915Notes

Reaction equation

HRID 1008915 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][C:14](=[O:16])[O:13][C:12](=O)[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:18][NH2:19]>C1COCC1>[CH3:18][N:19]1[C:14](=[O:16])[CH2:15][CH:10]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:11][C:12]1=[O:13]

Participants

4

Reactant 2

HCID 6329MethylamineHCID 178879674-(4-Nitrophenyl)oxane-2,6-dione

Product 1

HCID 597712961-Methyl-4-(4-nitrophenyl)piperidine-2,6-dioneYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 399 mg (1.70 mmol) of 4-(4-nitro-phenyl)-dihydro-pyran-2,6-dione (as prepared in Example 2, step (b)) in THF (8 mL) was treated with 1.10 mL (2.21 mmol) of 2.0 M methylamine in THF. The mixture was stirred at RT for 45 min, concentrated in vacuo, taken up in 1 N aqueous HCl (10 mL), and extracted with EtOAc (2×20 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was taken up in acetic anhydride (7 mL), treated with triethylamine (1 mL) and heated to 80° C. for 1 h. The solvents were removed in vacuo. The residue was taken up in EtOAc (20 mL) and washed successively with 1 N aqueous HCl, saturated aqueous NaHCO3, and water (1×10 mL each). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue with 25-50% EtOAc-hexane afforded 348 mg (83%) of the title compound as an off-white solid: 1H-NMR (CDCl3; 400 MHz): δ 8.25 (d, 2H, J=8.8 Hz), 7.40 (d, 2H, J=8.8 Hz), 3.56-3.45 (m, 1H), 3.21 (s, 3H), 3.10-3.01 (m, 2H), 2.88-2.77 (m, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. additiontreated with triethylamine (1 mL)
  6. temperatureheated to 80° C. for 1 h
  7. customThe solvents were removed in vacuo
  8. washwashed successively with 1 N aqueous HCl, saturated aqueous NaHCO3, and water (1×10 mL each)
  9. dry with materialThe organic layer was dried (MgSO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4b5507bdb73346f2b52c059f53332752
Source dataset
uspto-grants-2011_07
Patent number
US07973035B2

Reaction notes

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