Diethyl Oxalate → 3-[5-(2-Benzyloxy-ethoxy)-2-nitro-phenyl]-2-oxo-propionic acid ethyl ester

HRID 1955254Notes

Reaction equation

HRID 1955254 reaction equation
[H-].[Na+].[C:3](OCC)(=[O:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:13][C:14]1[CH:19]=[C:18]([O:20][CH2:21][CH2:22][O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:17]=[CH:16][C:15]=1[N+:31]([O-:33])=[O:32].[H][H]>C1COCC1.C(O)C>[CH2:7]([O:6][C:4](=[O:5])[C:3](=[O:9])[CH2:13][C:14]1[CH:19]=[C:18]([O:20][CH2:21][CH2:22][O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:17]=[CH:16][C:15]=1[N+:31]([O-:33])=[O:32])[CH3:8]

Participants

7

Reactant 4

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 232945584-(2-(Benzyloxy)ethoxy)-2-methyl-1-nitrobenzeneHCID 178418361HCID 178418361, compound

Product 1

HCID 538942143-[5-(2-Benzyloxy-ethoxy)-2-nitro-phenyl]-2-oxo-propionic acid ethyl esterYield 72.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (1.62 g, 60%, 40.5 mmol) in 20 ml of anhydrous THF at room temperature was added ethanol (2.5 ml) slowly. Diethyl oxalate (5.5 ml, 40.50 mmol) and 2-methyl-1-nitro-4-[2-(phenylmethoxy)ethoxy]benzene (10.19 g, 35.49 mmol) was added to the solution slowly after hydrogen evolution subsided. The reaction was heated at 60° C. for 2 h. The deep red solution was cooled to 0° C. and quenched with 50 ml of 3N HCl solution. Brine (50 ml) was added and the mixture was extracted with EtOAc (2×100 ml). The combined organic layers was dried with MgSO4, filtered and concentrated. The brown oil was chromatographed on silica gel with 20% ethyl acetate in hexanes to elute out starting material and then with 35% ethyl acetate in hexanes to give 9.93 g (72%) of 3-[5-(2-benzyloxy-ethoxy)-2-nitro-phenyl]-2-oxo-propionic acid ethyl ester as a yellow oil. 1H NMR (CDCl3) 8.18 (1H, d, J=9.29), 7.35-7.25 (5H, m), 6.91 (1H, dd, J=9.29, 2.69), 6.77 (1H, d, J=2.69), 4.59 (2H, s), 4.44 (2H, s), 4.35 (2H, q, J=7.32), 4.19 (2H, m), 3.81 (2H, m), 1.37 (3H, t, J=7.32).

Workup

  1. temperatureThe deep red solution was cooled to 0° C.
  2. customquenched with 50 ml of 3N HCl solution
  3. additionBrine (50 ml) was added
  4. extractionthe mixture was extracted with EtOAc (2×100 ml)
  5. dry with materialThe combined organic layers was dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe brown oil was chromatographed on silica gel with 20% ethyl acetate in hexanes
  9. washto elute out

Sources & evidence

ORD record
ord-75a458bca73d4bd581c4fa8aa561f7dc
Source dataset
uspto-grants-2000_09
Patent number
US06124323

Reaction notes

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