Methyl iodide → 4-tert-Butyl 1-methyl N-[(benzyloxy)carbonyl]-L-aspartate

HRID 446897Notes

Reaction equation

HRID 446897 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].O.[C:25]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[CH3:25][O:12][C:11](=[O:13])[C@@H:2]([NH:1][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:3][C:4]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:10]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 74892349Z-Asp(OtBu)-OH·H2O

Product 1

HCID 105930224-tert-Butyl 1-methyl N-[(benzyloxy)carbonyl]-L-aspartate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To Cbz-Asp(O-tert-Bu)-OH.H2O (5.00 g, 14.6 mmol) and K2CO3 (4.05 g, 2.0 eq) were added DMF (100 mL) and MeI (2.74 mL, 3 eq), which was then stirred for 2-3 h at room temperature. The solvent was distilled under reduced pressure. The residue was extracted with ethyl acetate (100 mL×2), washed with water, aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution, dried (anhydrous Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography (30% ethyl acetate/hexane) to give (S)-2-benzyloxycarbonylamino-succinic acid 4-tert-butyl ester 1-methyl ester in a stoichiometric yield. This compound was dissolved in MeOH (100 mL), c-HCl (1.1 mL, 1.0 eq) was added, and subjected to debenzyloxycarbonylation (Pd/C) for 40 min under hydrogen balloon, whereby giving 3.28 g (96%) of the title compound.

Workup

  1. distillationThe solvent was distilled under reduced pressure
  2. extractionThe residue was extracted with ethyl acetate (100 mL×2)
  3. washwashed with water, aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution
  4. dry with materialdried (anhydrous Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6421b86a15ed4f41ac9470bf81dc7d29
Source dataset
uspto-grants-2013_07
Patent number
US08481537B2

Reaction notes

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