Sulfuric Acid → Methyl 4-(furan-2-yl)-2,4-dioxobutanoate

HRID 1054302Notes

Reaction equation

HRID 1054302 reaction equation
[Na].[C:2]([C:5]1[O:6][CH:7]=[CH:8][CH:9]=1)(=[O:4])[CH3:3].[C:10](OCC)(=[O:16])[C:11]([O:13][CH2:14]C)=[O:12].OS(O)(=O)=O>CO>[O:6]1[CH:7]=[CH:8][CH:9]=[C:5]1[C:2](=[O:4])[CH2:3][C:10](=[O:16])[C:11]([O:13][CH3:14])=[O:12]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 7268Diethyl OxalateHCID 145052-AcetylfuranHCID 5360545Sodium

Product 1

HCID 2771615Methyl 4-(furan-2-yl)-2,4-dioxobutanoateYield 35.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

(see, e.g., Ghosh, A. K., et al., J Med Chem 2005, 48, 6767-71). To a stirred solution of MeOH (150 mL) at room temperature under nitrogen, freshly cut Na (1.81 g, 78.7 mmol) was added in pieces and with care. After all the sodium dissolved, a mixture of 2-acetylfuran (6 mL, 59.8 mmol) and diethyl oxalate (8.14 mL, 59.9 mmol) was added dropwise over a period of 3 min at room temperature. The resulting mixture was continued to stir. Brown precipitates formed after 20 min stir. The mixture was stirred for a total of 1 h. The reaction mixture was cooled to 0° C., and a mixture of concentrated H2SO4 and ice was added. Some solid precipitated at this point which was filtered off but was not the desired product by 1H NMR. The filterate was extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude was recrystallized from hot iPrOH to give the title compound (4.15 g, 35%) as a dark brown solid. 1H NMR (400 MHz, CDCl3) δ 7.67-7.65 (m, 1H), 7.33 (d, J=3.6 Hz, 1H), 6.93 (s, 1H), 6.60 (dd, J=3.5, 1.5 Hz, 1H), 3.91 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 181.01, 165.39, 162.43, 150.82, 147.73, 118.58, 113.14, 99.17, 53.18.

Workup

  1. additionwas added dropwise over a period of 3 min at room temperature
  2. customBrown precipitates
  3. customformed after 20 min
  4. stirringstir
  5. stirringThe mixture was stirred for a total of 1 h
  6. additionwas added
  7. customSome solid precipitated at this point which
  8. filtrationwas filtered off
  9. extractionThe filterate was extracted with CH2Cl2 (50 mL×2)
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude was recrystallized from hot iPrOH

Sources & evidence

ORD record
ord-ebf325d8d2e642cc872b666e0f2dd633
Source dataset
uspto-grants-2016_07
Patent number
US09394303B2

Reaction notes

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