Propargyl alcohol → 1-[4-(Difluoromethoxy)phenyl]-2-[3-(1,4-dihydroxybut-2-ynyl)phenyl]ethane-1,2-dione

HRID 30596Notes

Reaction equation

HRID 30596 reaction equation
[CH2:1]([OH:4])[C:2]#[CH:3].[Li]CCCC.[F:10][CH:11]([F:31])[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:30])[C:20]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[CH:25]=[O:26])=[O:21])=[CH:15][CH:14]=1>C1COCC1.COCCOC>[F:10][CH:11]([F:31])[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:30])[C:20]([C:22]2[CH:29]=[CH:28][CH:27]=[C:24]([CH:25]([OH:26])[C:3]#[C:2][CH2:1][OH:4])[CH:23]=2)=[O:21])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 597903033-[2-(4-Difluoromethoxyphenyl)-2-oxo-acetyl]benzaldehydeHCID 178418339Butyllithium

Product 1

HCID 686492321-[4-(Difluoromethoxy)phenyl]-2-[3-(1,4-dihydroxybut-2-ynyl)phenyl]ethane-1,2-dioneYield 29%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of propargyl alcohol (0.1 g, 1.78 mmol) in dry THF at −78° C. under nitrogen was treated dropwise with 1.9 M n-BuLi (1.88 mL, 3.57 mmol) over 10 min, stirred for 0.5 h and warmed to 0° C. A 3 mL portion of this solution was added to a stirred solution of 3-[2-(4-difluoromethoxyphenyl)-2-oxo-acetyl]benzaldehyde (0.15 g, 0.49 mmol) in dry DME at 0° C. under nitrogen. After 10 min, the reaction mixture was 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 (30% to 70% ethyl acetate/petroleum ether) gave 1-[4-(difluoromethoxy)phenyl]-2-[3-(1,4-dihydroxybut-2-ynyl)phenyl]ethane-1,2-dione as a clear oil, 52 mg (29% yield). Using essentially the same procedure described in Example 1, step c, and employing 1-[4-(difluoromethoxy)phenyl]-2-[3-(1,4-dihydroxybut-2-ynyl)phenyl]ethane-1,2-dione (0.052 g, 0.14 mmol), the title compound was obtained as a slight brown foam, 0.031 g (52% yield), identified by NMR and mass spectral analyses. MS (ES+): 416 (M+H).

Workup

  1. waitAfter 10 min
  2. customthe reaction mixture was quenched with saturated ammonium chloride
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the resultant residue by flash chromatography (30% to 70% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-b06db1c4157d499cb9340fa10473eb08
Source dataset
uspto-grants-2008_09
Patent number
US07423158B2

Reaction notes

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