Methyl 3-oxovalerate → Methyl 2-ethyl-5-[4-(trifluoromethyl)phenyl]-3-furoate

HRID 1876935Notes

Reaction equation

HRID 1876935 reaction equation
Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1)=[O:4].O=[C:16]([CH2:22][CH3:23])[CH2:17][C:18]([O:20][CH3:21])=[O:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:22]([C:16]1[O:4][C:3]([C:5]2[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=2)=[CH:2][C:17]=1[C:18]([O:20][CH3:21])=[O:19])[CH3:23]

Participants

5

Reactant 3

HCID 121699Methyl 3-oxovalerateHCID 521998p-Toluenesulfonic acid monohydrateHCID 127899772-Chloro-1-[4-(trifluoromethyl)phenyl]ethan-1-one

Product 1

HCID 23074458Methyl 2-ethyl-5-[4-(trifluoromethyl)phenyl]-3-furoateYield 29%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 2-chloro-4′-(trifluoromethyl)acetophenone (50.9 g) and methyl 3-oxopentanoate (25 g) in toluene (500 mL) was added dropwise 1,8-azabicyclo[5.4.0]-7-undecene (28.7 mL) under ice-cooling over 30 min or longer. After the completion of the dropwise addition, and the mixture was stirred under ice-cooling for 30 min, and at room temperature for 2 hr. The resulting precipitate was filtered, and washed with toluene. The obtained toluene solution was passed through silica gel, and the silica gel was washed with ethyl acetate-hexane (1:1). The collected solution was concentrated under reduced pressure to remove ethyl acetate-hexane to give a toluene solution. To this toluene solution was added 4-toluenesulfonic acid monohydrate (7.2 g), and the mixture was stirred at 100° C. for 2 hr. The reaction mixture was washed with aqueous sodium hydrogen carbonate solution, and the aqueous layer was extracted with ethyl acetate. The organic layer was collected, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (0% ethyl acetate/hexane to 10% ethyl acetate/hexane), and crystallized from ethyl acetate/hexane to give the title compound (16.3 g, 29%) as a white solid.

Workup

  1. temperaturecooling over 30 min or longer
  2. additionAfter the completion of the dropwise addition
  3. temperaturecooling for 30 min
  4. filtrationThe resulting precipitate was filtered
  5. washwashed with toluene
  6. washthe silica gel was washed with ethyl acetate-hexane (1:1)
  7. concentrationThe collected solution was concentrated under reduced pressure
  8. customto remove ethyl acetate-hexane
  9. customto give a toluene solution
  10. stirringthe mixture was stirred at 100° C. for 2 hr
  11. washThe reaction mixture was washed with aqueous sodium hydrogen carbonate solution
  12. extractionthe aqueous layer was extracted with ethyl acetate
  13. customThe organic layer was collected
  14. dry with materialdried over magnesium sulfate
  15. customThe solvent was evaporated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (0% ethyl acetate/hexane to 10% ethyl acetate/hexane)
  17. customcrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-6f8391de85af488797270fb411ecb66c
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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