2-(3,4,5-Trimethoxyphenyl)furan → 2-Methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(5-(3,4,5-trimethoxyphenyl)furan-2-yl)ethanone

HRID 2359219Notes

Reaction equation

HRID 2359219 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[O:14][CH:15]=[CH:16][CH:17]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C([Li])CCC.CON(C)[C:26](=[O:42])[CH:27]([O:40][CH3:41])[C:28]1[CH:33]=[CH:32][C:31]([C:34]2[O:35][C:36]([CH3:39])=[N:37][N:38]=2)=[CH:30][CH:29]=1>C1COCC1>[CH3:41][O:40][CH:27]([C:28]1[CH:29]=[CH:30][C:31]([C:34]2[O:35][C:36]([CH3:39])=[N:37][N:38]=2)=[CH:32][CH:33]=1)[C:26]([C:15]1[O:14][C:13]([C:5]2[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:17][CH:16]=1)=[O:42]

Participants

5

Reactant 3

HCID 508768262-(3,4,5-Trimethoxyphenyl)furanHCID 58432086N,2-dimethoxy-N-methyl-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetamideHCID 178418339Butyllithium

Product 1

HCID 533781142-Methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(5-(3,4,5-trimethoxyphenyl)furan-2-yl)ethanoneYield 29.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(3,4,5-trimethoxyphenyl)furan (1.4 g, 5.98 mmol) in anhydr THF (70 mL) under argon in an oven-dried flask cooled to −78° C. was added n-butyl lithium (2.5 M in hexanes; 2.63 mL, 6.28 mmol) dropwise. After stirring for 1 hr at −78° C., a solution of N,2-dimethoxy-N-methyl-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetamide (1.75 g, 6.0 mmol) in THF (5 mL) was added dropwise. After stirring for 25 min, the mixture was allowed to warm to room temp while stirring for 2 hrs. The reaction was quenched with the addition of saturated aqueous NH4Cl then brine and EtOAc were added. The layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography (60% EtOAc-hexanes) gave 2-methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(5-(3,4,5-trimethoxyphenyl)furan-2-yl)ethanone as a fluffy yellow solid (0.81 g, 29% yield). MS: m/z 465.3 [M+H]+.

Workup

  1. stirringAfter stirring for 25 min
  2. temperatureto warm to room temp
  3. stirringwhile stirring for 2 hrs
  4. customThe reaction was quenched with the addition of saturated aqueous NH4Cl
  5. additionbrine and EtOAc were added
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (60% EtOAc-hexanes)

Sources & evidence

ORD record
ord-2486f54c7fd84b21865601f1fda6182a
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

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