Malonic Acid → 4-nitrobenzyl 4-[(2R,3S)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoate

HRID 235742Notes

Reaction equation

HRID 235742 reaction equation
[CH3:1][C:2]([C@H:18]1[C:21](=[O:22])[NH:20][C@@H:19]1[CH2:23]C(O)=O)([O:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1)=[O:6])[CH3:3].[C:27]([OH:33])(=[O:32])[CH2:28][C:29]([OH:31])=O>O1CCCC1>[CH3:1][C:2]([C@H:18]1[C:21](=[O:22])[NH:20][C@@H:19]1[CH2:23][C:29](=[O:31])[CH2:28][C:27]([O:33][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1)=[O:32])([O:4][C:5]([O:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=1)=[O:6])[CH3:3]

Participants

4

Reactant 2

HCID 867Malonic AcidHCID 56618986{(2R,3S)-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-4-oxoazetidin-2-yl}acetic acid

Product 1

HCID 867388734-nitrobenzyl 4-[(2R,3S)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoateYield 153.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [(2R,3S)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-acetic acid (56.4 mg) in tetrahydrofuran (1.13 ml) was added N,N'-carbonyldiimidazole (27.5 mg) at ambient temperature. After stirring for 6 hours at ambient temperature, the magnesium salt of the mono-p-nitrobenzyl ester of malonic acid (84.8 mg) was added and the resulting mixture was stirred overnight at ambient temperature. The solvent was distilled off and the residue was dissolved in ethyl acetate (30 ml) and filtered with a diatomaceous earth. The filtrate was washed with 1N hydrochloric acid, water, phosphate buffer solution (pH 6.8), and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residual oil (78.8 mg) was chromatographed on silica gel (1.6 g) eluting with a mixture of methylene chloride and ethyl acetate (10:1 to 2:1) to give 4-nitrobenzyl 4-[(2R,3S)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoate (64.2 mg) as an amorphous solid.

Workup

  1. stirringthe resulting mixture was stirred overnight at ambient temperature
  2. distillationThe solvent was distilled off
  3. dissolutionthe residue was dissolved in ethyl acetate (30 ml)
  4. filtrationfiltered with a diatomaceous earth
  5. washThe filtrate was washed with 1N hydrochloric acid, water, phosphate buffer solution (pH 6.8), and saturated aqueous sodium chloride
  6. dry with materialAfter drying over magnesium sulfate
  7. extractionthe ethyl acetate extract
  8. filtrationwas filtered
  9. customevaporated in vacuo
  10. customThe residual oil (78.8 mg) was chromatographed on silica gel (1.6 g)
  11. washeluting with a mixture of methylene chloride and ethyl acetate (10:1 to 2:1)

Sources & evidence

ORD record
ord-fcc21f3152474009b486d598a3c3ea67
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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