Phenol → Deschloroclofibrate

HRID 1766113Notes

Reaction equation

HRID 1766113 reaction equation
CC(C)([O-])C.[K+].[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:14]([O:16][C:17](=[O:22])[C:18](Br)([CH3:20])[CH3:19])[CH3:15]>C1COCC1>[CH3:19][C:18]([O:13][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:20])[C:17]([O:16][CH2:14][CH3:15])=[O:22]

Participants

5

Reactant 3

HCID 996PhenolHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 86476DeschloroclofibrateYield 83.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of potassium t-butoxide (1M in THF, 531 ml, 0.531 moles, 1 eq) precooled to 0° C. (ice bath) was added phenol (50 g, 0.531 moles, 1 eq) in dry THF (50 ml) dropwise via an addition funnel over 20 minutes maintaining the internal temperature of the reaction below 5 degrees centigrade. Ethyl-2-bromoisobutyrate (70.14 ml, 0.9 eq, 0.478 moles) in dry THF (20 ml) was added dropwise over 10 minutes maintaining the internal reaction temperature below 5° C. After the addition was complete, the ice bath was removed and the reaction was allowed to warm to room temperature. The reaction was brought to reflux and maintained at this reflux temperature for 8 hours. Following the cooling of the reaction to 0° C. the volatiles were removed in vacuo. The residue was then partitioned between EtOAc and 1N NaOH. The phases were separated and the organic phase was washed with 1N NaOH, H2O, brine and dried over Na2SO4. After filtration the solution was concentrated under reduced pressure to yield 83 g (75%) of clean title compound.

Workup

  1. customprecooled to 0° C.
  2. temperaturemaintaining
  3. customthe internal temperature of the reaction below 5 degrees centigrade
  4. temperaturemaintaining the internal reaction temperature below 5° C
  5. additionAfter the addition
  6. customthe ice bath was removed
  7. temperatureto reflux
  8. temperaturemaintained at this reflux temperature for 8 hours
  9. temperaturecooling of the reaction to 0° C. the volatiles
  10. customwere removed in vacuo
  11. customThe residue was then partitioned between EtOAc and 1N NaOH
  12. customThe phases were separated
  13. washthe organic phase was washed with 1N NaOH, H2O, brine
  14. dry with materialdried over Na2SO4
  15. filtrationAfter filtration the solution
  16. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-e19a7420979a4f41af9ec5c72ab2b44d
Source dataset
uspto-grants-2007_06
Patent number
US07229998B2

Reaction notes

Loading…