Bis-(1H-imidazol-2-YL)-methanone → (S)-2-Benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-tert-butyl ester 1-methyl ester

HRID 1455570Notes

Reaction equation

HRID 1455570 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C@H:4]([CH2:16][C:17]([OH:19])=O)[NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].C(C1NC=CN=1)(C1NC=CN=1)=O.[C:33]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])(=[O:38])[CH2:34]C([O-])=O>O1CCCC1>[CH3:1][O:2][C:3](=[O:20])[C@@H:4]([NH:5][C:6]([O:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:7])[CH2:16][C:17](=[O:19])[CH2:34][C:33]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38]

Participants

5

Reactant 3

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 7021783Z-Asp-OMeHCID 21883978Tert-butyl malonate

Product 1

HCID 57535371(S)-2-Benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-tert-butyl ester 1-methyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-CBZ L-aspartic acid 1-methyl ester (1.00 g, 3.55 mmol) in dry tetrahydrofuran (17 mL) is added carbonyl diimidazole (634.1 mg, 3.91 mmol). The mixture is stirred at room temperature for 6 hr then the magnesium salt of mono-tert butyl malonate (1.339 g, 3.91 mmol) (prepared according to Angew. Chem. Int. Ed. Engl. 1979, 18(1), 72-74) is added. The mixture is stirred at room temperature for another 20 h, then concentrated in vacuum. The residue is partitioned between ether (60 mL) and 0.5 N HCl (60 mL). The organic layer is washed with saturated NaHCO3 solution (50 mL) then dried over magnesium sulfate and concentrated in vacuum. The residue is purified over 35 g of silica gel, eluted with EtOAc:Heptane (1:1) to afford (S)-2-Benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-tert-butyl ester 1-methyl ester (1.17 g, 87%).

Workup

  1. stirringThe mixture is stirred at room temperature for another 20 h
  2. concentrationconcentrated in vacuum
  3. customThe residue is partitioned between ether (60 mL) and 0.5 N HCl (60 mL)
  4. washThe organic layer is washed with saturated NaHCO3 solution (50 mL)
  5. dry with materialthen dried over magnesium sulfate
  6. concentrationconcentrated in vacuum
  7. customThe residue is purified over 35 g of silica gel
  8. washeluted with EtOAc:Heptane (1:1)

Sources & evidence

ORD record
ord-c41057ce537c4b0eadf8e34d68308ee8
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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