Diethyl Oxalate → (5S)-5-(1-methylethyl)-1-(phenylmethyl)-2,3-piperazinedione

HRID 419670Notes

Reaction equation

HRID 419670 reaction equation
[NH2:1][C@@H:2]([CH:12]([CH3:14])[CH3:13])[CH2:3][NH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:15](OCC)(=[O:21])[C:16](OCC)=[O:17]>CCO>[CH3:13][CH:12]([C@H:2]1[CH2:3][N:4]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:16](=[O:17])[C:15](=[O:21])[NH:1]1)[CH3:14]

Participants

4

Reactant 2

HCID 7268Diethyl OxalateHCID 44889995[(2S)-2-Amino-3-methylbutyl](phenylmethyl)amine

Product 1

HCID 59452588(5S)-5-(1-methylethyl)-1-(phenylmethyl)-2,3-piperazinedioneYield 74%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

[(2S)-2-Amino-3-methylbutyl](phenylmethyl)amine (Katritzky, A. R. Tetrahedron: Asymmetry 2002, 13, 933-938) (2.57 g, 13.4 mmol) was dissolved in 100 mL of EtOH with stirring. Diethyl oxalate (1.82 mL, 13.4 mmol) was added via syringe. The mixture was heated to reflux for 3.5 days and subsequently cooled to rt. The mixture was concentrated in vacuo. Purification by flash chromatography afforded the title compound of step A (2.43 g, 9.87 mmol, 74%). 1H NMR (400 MHz, DMSO-d6) δ 8.74 (br. s, 1H), 7.38-7.24 (m, 5H), 4.54 (AB, ΔνAB=88.7 Hz, JAB=14.7 Hz, 2H), 3.48 (dd, J=13.2, 4.2 Hz, 1H), 3.31 (dd, J=13.2, 6.2 Hz, 1H), 3.17 (m, 1H), 1.61 (m, 1H), 0.82 (d, J=6.8 Hz, 3H), 0.63 (d, J=6.8 Hz, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 3.5 days
  3. concentrationThe mixture was concentrated in vacuo
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-a1ace0d2d16d4d6fb9afbe66a73863f4
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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