Diethyl Oxalate → ETHYL 4-(4-BENZYLOXYPHENYL)-2,4-DIOXOBUTANOATE

HRID 1093628Notes

Reaction equation

HRID 1093628 reaction equation
[H-].[Na+].[C:3]([O:10][CH2:11][CH3:12])(=[O:9])[C:4]([O:6]CC)=O.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27](=[O:29])[CH3:28])=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[CH2:11]([O:10][C:3](=[O:9])[C:4](=[O:6])[CH2:28][C:27]([C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:22][CH:23]=1)=[O:29])[CH3:12]

Participants

5

Reactant 3

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 2452261-[4-(Benzyloxy)phenyl]ethan-1-one

Product 1

HCID 12242177ETHYL 4-(4-BENZYLOXYPHENYL)-2,4-DIOXOBUTANOATEYield 147%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-hydroxy-phenyl)-ethanone (10 g, 0.0735 mole) in DMF (50 mL) was added K2CO3 (20.2 g, 0.147 mole) at ambient temperature. Benzyl bromide (13.83 g, 0.0808 mole) was then added and the resulting mixture was stirred at ambient temperature for 5 hours. The reaction mixture was then quenched with iced water. The resulting precipitate was isolated by filtration and dried to afford 16.2 g (98%) of 1-(4-benzyloxy-phenyl)-ethanone. LCMS: 227.1 (M+1)+, 98.38%. A mixture of THF (130 mL) and NaH (60% w/w dispersion in oil) (5.28 g, 0.132 mole) was cooled to 0° C. with stirring for 5 minutes. Diethyl oxalate (12.87 g, 0.0886 mole) was added and the mixture was heated to reflux for 15 minutes. after cooling to ambient temperature 1-(4-benzyloxy-phenyl)-ethanone (10 g, 0.0442 mole) in THF (50 mL) was added dropwise over a period of 45 minutes. The resulting mixture was heated to 70° C. for 1 hour. The reaction mixture was then quenched with cold aqueous NH4Cl solution. The resulting precipitate was isolated by filtration and dried to afford 21.2 g of 4-(4-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester. LCMS: 327.12 (M+1)+, 36.5%. A solution of 4-(4-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester (10 g, 0.03064 mole), acetic acid (20 mL) and hydrazine hydrate (1.685 g, 0.0337 mole) was heated to reflux for 8 hours. The reaction mixture was then poured into iced water and basified with saturated aqueous NaHCO3 solution. The product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 6.3 g (64%) of 5-(4-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester. LCMS: 323.13 (M+1)+, 95.10%.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 15 minutes
  3. additionwas added dropwise over a period of 45 minutes
  4. temperatureThe resulting mixture was heated to 70° C. for 1 hour
  5. customThe reaction mixture was then quenched with cold aqueous NH4Cl solution
  6. customThe resulting precipitate was isolated by filtration
  7. customdried

Sources & evidence

ORD record
ord-5740859d71684ef58af1081235a317e5
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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