Diethyl Oxalate → (5-Fluorobenzofur-7-yl)oxoacetic acid ethyl ester

HRID 1824956Notes

Reaction equation

HRID 1824956 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.[Mg].[C:13](OCC)(=[O:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15]>BrCCBr.C(OCC)C.O1CCCC1.C(OCC)(=O)C>[O:19]=[C:13]([C:4]1[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=[C:2]([F:1])[CH:3]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

8

Reactant 3

HCID 7268Diethyl OxalateHCID 5462224MagnesiumHCID 221448167-Bromo-5-fluoro-1-benzofuran

Product 1

HCID 22144925(5-Fluorobenzofur-7-yl)oxoacetic acid ethyl esterYield 80.2%

Reagents, catalysts & solvents 4

HCID 78391,2-DibromoethaneCatalystHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1.01 gm (4.72 mMol) 5-fluoro-7-bromobenzofuran, 0.15 gm (6.14 mMol) magnesium(0), and 2 drops of 1,2-dibromoethane in 1 mL diethyl ether was stirred at room temperature until initiation of the Grignard formation had occurred (about 5–10 minutes). The mixture was then diluted with 8 mL of diethyl ether and heated at reflux for 30 minutes. This mixture was then added dropwise to a solution of 1.38 gm (9.44 mMol) diethyl oxalate in 3 mL tetrahydrofuran at −10° C. Once the addition was complete the reaction mixture was allowed to warm to room temperature and was then stirred at room temperature for 30 minutes. The reaction mixture was diluted with 20 volumes of ethyl acetate and was washed sequentially with 1N hydrochloric acid, water, and saturated aqueous sodium chloride. The remaining organics were concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with hexane containing 30% ethyl acetate. Fractions containing the desired product were combined and concentrated under reduced pressure to provide 0.894 gm (80%) of the desired compound.

Workup

  1. custom(about 5–10 minutes)
  2. temperatureheated
  3. temperatureat reflux for 30 minutes
  4. additionOnce the addition
  5. temperatureto warm to room temperature
  6. stirringwas then stirred at room temperature for 30 minutes
  7. washwas washed sequentially with 1N hydrochloric acid, water, and saturated aqueous sodium chloride
  8. concentrationThe remaining organics were concentrated under reduced pressure
  9. washeluting with hexane containing 30% ethyl acetate
  10. additionFractions containing the desired product
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cadc69615e314f26afde32b8095d1407
Source dataset
uspto-grants-2006_05
Patent number
US07045545B1

Reaction notes

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