Propanedioic acid, mono[(4-nitrophenyl)methyl] ester → 4-nitrobenzyl 4-[(2R,3R)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoate

HRID 1719332Notes

Reaction equation

HRID 1719332 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]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=1)(=[O:32])[CH2:28][C:29]([O-])=[O:30]>O1CCCC1>[CH3:1][C:2]([C@@H:18]1[C:21](=[O:22])[NH:20][C@@H:19]1[CH2:23][C:29](=[O:30])[CH2:28][C:27]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=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 18356643Propanedioic acid, mono[(4-nitrophenyl)methyl] esterHCID 54113415[(2R,3R)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-4-oxoazetidin-2-yl]acetic acid

Product 1

HCID 537224924-nitrobenzyl 4-[(2R,3R)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoateYield 83.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N,N'-Carbonyldiimidazole (540 mg) was added to a solution of [(2R,3R)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)-ethyl}-4-oxoazetidin-2-yl]acetic acid (1.06 g) in tetrahydrofuran (50 ml) at ambient temperature. After stirring for 7 hours at the same temperature, magnesium salt of mono-p-nitrobenzyl malonate (1.45 g) was added thereto, and the resultant mixture was stirred overnight at ambient temperature. The solvent was distilled off in vacuo. The residue was dissolved in ethyl acetate (100 ml) and filtered. The filtrate was washed in turn with 0.1N hydrochloric acid, water, saturated aqueous sodium chloride, aqueous sodium bicarbonate, water, saturated aqueous sodium chloride, 5% aqueous citric acid, water and saturated aqueous sodium chloride. After drying over magnesium sulfate, the solution was evaporated. The residue was chromatographed on silica gel (30 g) eluting with a mixture of methylene chloride and ethyl acetate (50:1 to 2:1) to give formy substance, which was crystallized from a mixture of chloroform and diisopropyl ether, washed with diisopropyl ether and then dried in vacuo to give 4-nitrobenzyl 4-[(2R,3R)-3-{1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl}-4-oxoazetidin-2-yl]-3-oxobutanoate (1.31 g), mp 123°-125° C. (dec.).

Workup

  1. additionwas added
  2. distillationThe solvent was distilled off in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (100 ml)
  4. filtrationfiltered
  5. washThe filtrate was washed in turn with 0.1N hydrochloric acid, water, saturated aqueous sodium chloride, aqueous sodium bicarbonate, water, saturated aqueous sodium chloride, 5% aqueous citric acid, water and saturated aqueous sodium chloride
  6. dry with materialAfter drying over magnesium sulfate
  7. customthe solution was evaporated
  8. customThe residue was chromatographed on silica gel (30 g)
  9. washeluting with a mixture of methylene chloride and ethyl acetate (50:1 to 2:1)
  10. customto give formy substance, which
  11. customwas crystallized from a mixture of chloroform and diisopropyl ether
  12. washwashed with diisopropyl ether
  13. customdried in vacuo

Sources & evidence

ORD record
ord-19a99ca7f9cc4a0884b33f3b6627a920
Source dataset
uspto-grants-1985_09
Patent number
US04539152

Reaction notes

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