Bromomethyl 4-methoxyphenyl ketone → HCID 68514199, compound

HRID 1877129Notes

Reaction equation

HRID 1877129 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)=[O:4].O=[C:14]([CH2:20][CH3:21])[CH2:15][C:16]([O:18][CH3:19])=[O:17].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:20]([C:14]1[O:4][C:3]([C:5]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=2)=[CH:2][C:15]=1[C:16]([O:18][CH3:19])=[O:17])[CH3:21]

Participants

5

Reactant 3

HCID 4965Bromomethyl 4-methoxyphenyl ketoneHCID 121699Methyl 3-oxovalerateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 68514199HCID 68514199, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 2-bromo-4′-methoxyacetophenone (13.7 g) and methyl 3-oxopentanoate (7.8 g) in toluene (100 mL) was added dropwise 1,8-azabicyclo[5.4.0]-7-undecene (9.1 mL) over 30 min or more under ice-cooling. After the completion of the dropwise addition, the mixture was stirred for 30 min under ice-cooling, and then 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 solutions were concentrated under reduced pressure to remove ethyl acetate-hexane to give a toluene solution. To this toluene solution was added 4-toluenesulfonic acid monohydrate (2.3 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 layers were 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 5% ethyl acetate/hexane) to give the title compound (9.2 g, 59%) as an oil.

Workup

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

Sources & evidence

ORD record
ord-d247e209cb9945a897f7c8c5b3c3ffc1
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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