Diethyl Oxalate → 6-(4-chlorophenyl)-2,4-dioxohexanoic Acid Ethyl Ester

HRID 1434774Notes

Reaction equation

HRID 1434774 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12](=[O:14])[CH3:13])=[CH:6][CH:5]=1.[CH2:15]([O:17][C:18](=[O:24])[C:19](OCC)=[O:20])[CH3:16].CC[O-].[Na+]>CCO>[CH2:15]([O:17][C:18](=[O:24])[C:19](=[O:20])[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][C:7]1[CH:6]=[CH:5][C:4]([Cl:3])=[CH:9][CH:8]=1)[CH3:16]

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 2192774-(4-Chlorophenyl)butan-2-oneHCID 2723922Sodium ethoxide

Product 1

HCID 574351006-(4-chlorophenyl)-2,4-dioxohexanoic Acid Ethyl EsterYield 46.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium hydride (0.4163 g, 17.35 mmol) was added slowly to a NaCl ice bath containing EtOH (5.3 mL, 2.5 M) stirring under N2. 66 (2.4253 g, 13.28 mmol) and diethyloxalate (1.803 g, 13.28 mmol) were mixed together, and then added to the chilled NaOEt solution. After stirring for 5 minutes, the reaction was warmed to room temperature. After 10 minutes, the reaction solidified and an additional 10 mL EtOH was added. After stirring for ˜5 h, the reaction was quenched at 0° C. with 1N HCl and extracted 2× with CH2Cl2. The combined organics were washed with H2O, dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 1:1 Hexanes:CH2Cl2): Only pure fractions were combined and concentrated to obtain 67 (1.7561 g, 46.8%): 1H (CDCl3, 400 MHz): δ 14.27 (1H, broad s), 7.22 (2H, d, J=8.3 Hz), 7.10 (2H, d, J=8.3 Hz), 6.32 (1H, s), 4.31 (2H, q, J=7.2 Hz), 2.92 (2H, t, J=7.8 Hz), 2.78 (2H, t, J=7.8 Hz), 1.34 (3H, t, J=7.2 Hz) ppm. 13C (CDCl3, 100 MHz): δ 201.59, 166.07, 161.79, 138.51, 132.00, 128.53, 128.54, 101.72, 62.38, 42.08, 29.60, 13.88 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 13.88; CH2 carbons: 62.38, 42.08, 29.60; CH carbons: 129.53, 128.54, 101.72 ppm. HPLC: 11.103 min.

Workup

  1. stirringAfter stirring for 5 minutes
  2. stirringAfter stirring for ˜5 h
  3. customthe reaction was quenched at 0° C. with 1N HCl
  4. extractionextracted 2× with CH2Cl2
  5. washThe combined organics were washed with H2O
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (Combiflash column, 1:1 Hexanes:CH2Cl2)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-df6de9b5564444a8bfb0e27f6556296e
Source dataset
uspto-grants-2009_11
Patent number
US07615572B2

Reaction notes

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