Ibuprofen, (+-)- → Ethyl 2-[4-(2-methylpropyl)phenyl]propanoate

HRID 873287Notes

Reaction equation

HRID 873287 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH3:15])[C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].O.[C:17]1(C)C=CC(S(O)(=O)=O)=C[CH:18]=1>C1C=CC=CC=1.C(O)C>[CH2:17]([O:13][C:12](=[O:14])[CH:11]([C:8]1[CH:7]=[CH:6][C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:10][CH:9]=1)[CH3:15])[CH3:18]

Participants

5

Reactant 2

HCID 3672Ibuprofen, (+-)-HCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 170486Ethyl 2-[4-(2-methylpropyl)phenyl]propanoateYield 563.9%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 702EthanolSolvent

Procedure

A solution of 2-(4-isobutylphenyl)-propionoic acid (Ibuprofen, 9.6 g, 46.5 mmol) and p-toluenesulfonic acid monohydrate (1.52 g, 7.9 mmol) in benzene (100 mL) and ethanol (75 mL) was heated to reflux using a Dean-Stark apparatus for 4 h. The solvent was removed under reduced pressure and the residue was taken up in Et2O (100 mL). The solution was extracted with saturated aqueous NaHCO3 solution (2×100 mL) and water (2×100 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated, affording 204 (10.44 g, 96%) as a clear oil. 1H NMR (CDCl3): δ 7.19 (d, 2H, J=8.0), 7.08 (d, 2H, J=8.0), 4.10 (m, 2H), 3.66 (q, 1H, J=7.0), 2.44 (d, 2H, J=7.0), 1.84 (m, 1H), 1.47 (d, 3H, J=7.0), 1.19 (t, 3H, J=7.3), 0.89 (d, 6H, J=7.0). 13C NMR (CDCl3): δ 174.92, 140.59, 138.07, 129.45, 127.29, 60.79, 45.32, 45.21, 30.35, 22.55, 18.78, 14.29. HRMS (LSIMS, nba): Calcd for C15H23O2 (MH+): 235.1698, found: 235.1688.

Workup

  1. temperatureto reflux
  2. customfor 4 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe solution was extracted with saturated aqueous NaHCO3 solution (2×100 mL) and water (2×100 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f52a7fa6ecbb4eaca89a706fa03f6e17
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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