3-[2-(4-Difluoromethoxyphenyl)-2-oxo-acetyl]benzaldehyde → 1-(4-Difluoromethoxyphenyl)-2-[3-(1-hydroxybut-2-ynyl)phenyl]ethane-1,2-dione

HRID 30595Notes

Reaction equation

HRID 30595 reaction equation
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:21])[C:11]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH:16]=[O:17])=[O:12])=[CH:6][CH:5]=1.[C:23]([Mg]Br)#[C:24][CH3:25]>COCCOC.C1COCC1>[F:1][CH:2]([F:22])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:21])[C:11]([C:13]2[CH:20]=[CH:19][CH:18]=[C:15]([CH:16]([OH:17])[C:23]#[C:24][CH3:25])[CH:14]=2)=[O:12])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 597903033-[2-(4-Difluoromethoxyphenyl)-2-oxo-acetyl]benzaldehydeHCID 178419101HCID 178419101, compound

Product 1

HCID 686488621-(4-Difluoromethoxyphenyl)-2-[3-(1-hydroxybut-2-ynyl)phenyl]ethane-1,2-dioneYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A stirred solution of 3-[2-(4-difluoromethoxyphenyl)-2-oxo-acetyl]-benzaldehyde (0.1 g, 0.33 mmol) in dry DME at 0° C. under nitrogen was treated over 10 min with 0.5 M 1-propynyl magnesium bromide in THF. The reaction was stirred for 0.5 h, quenched with saturated ammonium chloride, diluted with water and extracted with ethyl acetate. The combined extracts were dried over MgSO4 and concentrated in vacuo. Purification of the resultant residue by flash chromatography (20% to 40% ethyl acetate/petroleum ether) gave 1-(4-difluoromethoxyphenyl)-2-[3-(1-hydroxybut-2-ynyl)phenyl]ethane-1,2-dione as a clear oil, 55 mg (49% yield). Using essentially the same procedure described as described in Example 1, step c, and employing 1-(4-difluoromethoxyphenyl)-2-[3-(1-hydroxy-but-2-ynyl)phenyl]-ethane-1,2-dione (0.055 g, 0.16 mmol), the title product was obtained as a slight yellow foam, 0.044 g (69% yield), identified by NMR and mass spectral analyses. MS (ES+): 400 (M+H).

Workup

  1. customquenched with saturated ammonium chloride
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the resultant residue by flash chromatography (20% to 40% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-3db253a134b2421b860ec8bb95540202
Source dataset
uspto-grants-2008_09
Patent number
US07423158B2

Reaction notes

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