Ethyl benzoylformate → Ethyl(4-tert-butyloxycarbonylphenyl)(hydroxy)phenylacetate

HRID 1058293Notes

Reaction equation

HRID 1058293 reaction equation
I[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.C([Mg]Br)(C)C.[C:20]([C:28]([O:30][CH2:31][CH3:32])=[O:29])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[C:9]([O:8][C:6]([C:5]1[CH:13]=[CH:14][C:2]([C:20]([OH:27])([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:3][CH:4]=1)=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 15349Ethyl benzoylformateHCID 11130493Tert-butyl 4-iodobenzoateHCID 178418365HCID 178418365, compound

Product 1

HCID 69939053Ethyl(4-tert-butyloxycarbonylphenyl)(hydroxy)phenylacetateYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a stirred solution of tert-butyl 4-iodobenzoate (0.304 g, 1.0 mmol) in 10 mL THF at −40° C. was added a solution of isopropylmagnesium bromide (1.05 ml, 1.05 mmol, 1M in THF) dropwise under argon. After stirring for 1 hour at −40° C., ethyl benzoylformate (0.175 ml, 1.1 mmol) was added dropwise and the cold bath allowed to warm to room temperature over a 40 min. period. The reaction was quenched by the addition of an aqueous solution of 20% ammonium chloride. The reaction mixture was extracted twice with ether, the combined organic layers washed with brine, dried over Na2SO4 and was evaporated to give an oil that was chromatographed on 10 g silica gel using a gradient elution from 0-40% EtOAc in Hexanes. Product containing fractions were combined and concentrated to give (0.078 g, 22%) ethyl (4-tert-butyloxycarbonylphenyl)(hydroxy)phenylacetate as a colorless oil. NMR, 400 MHz (CDCl3) 7.95 ppm (d, J=8.55 Hz, 2H), 7.52 ppm (d, J=8.55 Hz, 2H), 7.30-7.40 ppm (m, 5H), 4.33 ppm (q, J=7.08 Hz, 2H), 4.29 ppm (s, OH, 1H), 1.59 ppm (s, 9H), 1.28 ppm (t, J=7.08 Hz, 3H).

Workup

  1. temperatureto warm to room temperature over a 40 min. period
  2. customThe reaction was quenched by the addition of an aqueous solution of 20% ammonium chloride
  3. extractionThe reaction mixture was extracted twice with ether
  4. washthe combined organic layers washed with brine
  5. dry with materialdried over Na2SO4
  6. customwas evaporated
  7. customto give an oil that
  8. customwas chromatographed on 10 g silica gel using
  9. washa gradient elution from 0-40% EtOAc in Hexanes
  10. additionProduct containing fractions
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c91c20f903c8429bab9539f25ffa11a2
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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