4-Chlorophenol → Clofibrate

HRID 1850000

Reaction equation

HRID 1850000 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[K+].Br[C:12]([CH3:19])([CH3:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14]>C(O)C>[CH2:16]([O:15][C:13](=[O:14])[C:12]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([CH3:19])[CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 46844-ChlorophenolHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 14797Potassium Hydroxide

Product 1

HCID 2796ClofibrateYield 40.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 4-chlorophenol (3 g, 23.3 mmol) in ethanol (100 mL) at room temperature is added potassium hydroxide (1.3 g, 23.3 mmol). The suspension is warmed at ˜35° C. for 15 min to complete dissolution before ethyl α-bromoisobutyrate (3.46 mL, 23.3 mmol) is introduced. The reaction is then heated to reflux where it is maintained for 16 h. After this time, the mixture is cooled to room temperature and filtered. The collected solids are washed with additional ethanol (10 mL) and the combined filtrates are concentrated under reduced pressure. The residue is dissolved in DCM (60 mL) and washed with water (×2). The organic phase is dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a clear colourless liquid (2.30 g, 40%). 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 1.25 (3H, t, J=7.1 Hz), 1.58 (6H, s), 4.23 (2H, q, J=7.1 Hz), 6.78 (2H, d, J=9.0 Hz), 7.19 (2H, d, J=9.1 Hz); m/z: 243/245 [M+H+].

Workup

  1. additionis introduced
  2. temperatureThe reaction is then heated
  3. temperatureto reflux where it
  4. temperatureis maintained for 16 h
  5. temperatureAfter this time, the mixture is cooled to room temperature
  6. filtrationfiltered
  7. washThe collected solids are washed with additional ethanol (10 mL)
  8. concentrationthe combined filtrates are concentrated under reduced pressure
  9. dissolutionThe residue is dissolved in DCM (60 mL)
  10. washwashed with water (×2)
  11. dry with materialThe organic phase is dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-34fd3a8a3197410daff6438ae46c449d
Source dataset
uspto-grants-2015_02
Patent number
US08957063B2

Linked notes

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