3-Methoxyacetophenone → HCID 57799927, compound

HRID 2100646Notes

Reaction equation

HRID 2100646 reaction equation
[F:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:19](=[O:21])[CH3:20])[CH:16]=[CH:17][CH:18]=1.[OH-:22].[Na+]>ClCCl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:5]([CH2:20][C:19]([C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([O:12][CH3:11])[CH:14]=2)=[O:22])[CH2:20][C:19]([C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([O:12][CH3:11])[CH:14]=2)=[O:21])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 114603-MethoxyacetophenoneHCID 14798Sodium HydroxideHCID 27792353-Fluoro-2-methylbenzaldehyde

Product 1

HCID 57799927HCID 57799927, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-fluoro-2-methylbenzaldehyde (75.0 g, 543 mmol) and 3′-methoxyacetophenone (179 g, 1.32 mol) in dichloromethane (1.5 L) was added 10% aq NaOH (750 mL) and tetrabutylammonium bromide (30.8 g, 95.7 mmol) portion-wise using a water/ice bath to maintain room temperature. The resulting mixture was stirred vigorously at room temperature for 16 h during which time a precipitate formed. An additional portion of tetrabutylammonium bromide (10.0 g, 31.1 mmol) was added and the mixture stirred an additional 3 h. The layers were separated, the aqueous phase was extracted with dichloromethane (500 mL), and the combined organic phases were washed with water. The organic layer was then dried over MgSO4, filtered, and concentrated under vacuum to give 279.1 g of crude product as a viscous brown oil. Purification over silica gel using 25-50% EtOAc/hexanes followed by slurrying of the concentrated yellow oil with 50% ether/hexanes and 100% ether gave the desired product, 3-(3-fluoro-2-methylphenyl)-1,5-bis(3-methoxyphenyl)pentane-1,5-dione (71.6 g, 31.4% yield), (characterized by 1H NMR).

Workup

  1. customformed
  2. stirringthe mixture stirred an additional 3 h
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with dichloromethane (500 mL)
  5. washthe combined organic phases were washed with water
  6. dry with materialThe organic layer was then dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto give 279.1 g of crude product as a viscous brown oil
  10. customPurification over silica gel using 25-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-460ff68d006849d6b175b7c58a9ba95f
Source dataset
uspto-grants-2009_08
Patent number
US07572814B2

Reaction notes

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