Propanoic acid, 2-bromo-2-methyl-, ethyl ester → Deschloroclofibrate

HRID 270145

Reaction equation

HRID 270145 reaction equation
CC(C)([O-:4])C.[K+].BrCC1N=C([C:19]2[CH:24]=[CH:23][C:22](C(F)(F)F)=[CH:21][CH:20]=2)SC=1C(OCC)=O.[CH2:29]([O:31][C:32](=[O:37])[C:33](Br)([CH3:35])[CH3:34])[CH3:30]>C1COCC1>[CH3:34][C:33]([O:4][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)([CH3:35])[C:32]([O:31][CH2:29][CH3:30])=[O:37]

Participants

5

Reactant 3

HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 179517684-Bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic Acid Ethyl EsterHCID 23665647Potassium tert-butoxide

Product 1

HCID 86476Deschloroclofibrate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of potassium t-butoxide (1M in THF, 531ml, 0.531moles, 1eq) precooled to 0° C. (ice bath) was added phenol (50g, 0.531moles, 1eq) in dry THF (50ml) dropwise via an addition funnel over 20minutes maintaining the internal temperature of the reaction below 5degrees centigrade. Ethyl-2-bromoisobutyrate (70.14ml, 0.9eq, 0.478moles) in dry THF (20ml) was added dropwise over 10minutes 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 8hours. 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 washed with 1N NaOH, H2O, brine and dried over Na2SO4. After filtration the solution was concentrated under reduced pressure to yield 83g (75%) of clean title compound.

Workup

  1. customprecooled to 0° C.
  2. temperaturemaintaining
  3. customthe internal temperature of the reaction below 5degrees 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 8hours
  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 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-d9714ca98a264ab0bd2c3739f37971c8
Source dataset
uspto-grants-2008_11
Patent number
US07449468B2

Linked notes

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