2-(4-Chlorophenoxy)-2-methylpropanoyl chloride → Clofibric Acid

HRID 1461002Notes

Reaction equation

HRID 1461002 reaction equation
CC([Si](C)(C)[O:6]C1CC(CCC2C3C(=CC(C)CC3O)C=CC2C)OC(=O)C1)(C)C.[Cl:31][C:32]1[CH:44]=[CH:43][C:35]([O:36][C:37]([CH3:42])([CH3:41])[C:38](Cl)=[O:39])=[CH:34][CH:33]=1>N1C=CC=CC=1>[Cl:31][C:32]1[CH:44]=[CH:43][C:35]([O:36][C:37]([CH3:42])([CH3:41])[C:38]([OH:6])=[O:39])=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 27813122-(4-Chlorophenoxy)-2-methylpropanoyl chlorideHCID 12953852HCID 12953852, compound

Product 1

HCID 2797Clofibric Acid

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of [1S-[1α(4R*,6R*),2α,6β,8β,8aα]]-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-6-[2-(1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthalenyl)ethyl]tetrahydro-2H-pyran-2-one in an amount of 1.00 g (2.29 mmol), 18.6 ml of dry pyridine, 1.40 g (1.15 mmol) 4-N,N-dimethylaminopyridine and 5.34 g (22.9 mmol) of 2-(4-chlorophenoxy)-2-methylpropionyl chloride was heated at 50° C. for 63/4hour, then stirred overnight at room temperature. Ice chips were then added, and after 30 min the mixture was poured into ice water and extracted four times with diethylether. The combined ether layers were washed with water, then washed with 0.1M H2SO4 and then dried over a conventional drying agent, preferably anhydrous sodium sulfate. The mixture was filtered and volatiles removed under reduced pressure (i.e. below atmospheric pressure, preferably around 30 mm). The residue was dissolved in diethylether, washed with saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. The mixture was filtered and volatiles removed under reduced pressure to leave 1.6 of 2-(4-chlorophenoxy)-2-methylpropionic acid-[1S-[1α,3α,7β,8β(2R*,4R*),8aβ]]-8-[2[tetrahydro-4-[ [(1,1-dimethylethyl)dimethylsilyl]oxy]6-oxo-2H-pyran-2-yl]ethyl]-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl ester as a brown oil which was used directly without further purification.

Workup

  1. additionIce chips were then added
  2. extractionextracted four times with diethylether
  3. washThe combined ether layers were washed with water
  4. washwashed with 0.1M H2SO4
  5. dry with materialdried over a conventional drying agent, preferably anhydrous sodium sulfate
  6. filtrationThe mixture was filtered
  7. customvolatiles removed under reduced pressure (i.e. below atmospheric pressure, preferably around 30 mm)
  8. dissolutionThe residue was dissolved in diethylether
  9. washwashed with saturated sodium bicarbonate solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationThe mixture was filtered
  12. customvolatiles removed under reduced pressure

Sources & evidence

ORD record
ord-8578716a2c2d4f15b0c2c16fb795a50a
Source dataset
uspto-grants-1991_12
Patent number
US05073568

Reaction notes

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