5-(Benzyloxy)-3-methyl-1-benzofuran-2-carbaldehyde → 1-[5-(Benzyloxy)-3-methyl-1-benzofuran-2-yl]-3-methylbutan-1-ol

HRID 2091351Notes

Reaction equation

HRID 2091351 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH:17]=[O:18])=[C:14]([CH3:19])[C:13]=2[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([Mg]Br)[CH:22]([CH3:24])[CH3:23]>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH:17]([OH:18])[CH2:21][CH:22]([CH3:24])[CH3:23])=[C:14]([CH3:19])[C:13]=2[CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 866627535-(Benzyloxy)-3-methyl-1-benzofuran-2-carbaldehyde2×HCID 178418816HCID 178418816, compound

Product 1

HCID 667791391-[5-(Benzyloxy)-3-methyl-1-benzofuran-2-yl]-3-methylbutan-1-olYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution (15 mL) of 5-(benzyloxy)-3-methyl-1-benzofuran-2-carbaldehyde (1.2 g) synthesized in the above-mentioned (3) in tetrahydrofuran was added dropwise isobutylmagnesium bromide (1M, tetrahydrofuran solution) under ice-cooling. The ice bath was removed, the reaction mixture was stirred at room temperature for 15 min, and aqueous ammonium chloride solution was added to quench the reaction. The reaction mixture was extracted with ethyl acetate, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio) to give 1-[5-(benzyloxy)-3-methyl-1-benzofuran-2-yl]-3-methylbutan-1-ol (0.82 g, 56%) as a pale-yellow oil. This was dissolved in tetrahydrofuran (15 mL), and thionyl chloride (0.35 mL) was added to the solution at room temperature. The reaction mixture was stirred at room temperature for 30 min then ice-cooled, and saturated aqueous sodium hydrogen carbonate solution (15 mL) was carefully added to the mixture. The reaction mixture was stirred for 10 min, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylacetamide (15 mL), sodium iodide (0.56 g), sodium carbonate (0.38 g) and ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (0.63 g) synthesized in Example 2(2) were added to the solution, and the mixture was stirred at 80° C. for 12 hr. After allowing to cool, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give the title object compound (0.46 g, 33%) as a yellow oil.

Workup

  1. temperaturecooling
  2. customThe ice bath was removed
  3. additionaqueous ammonium chloride solution was added
  4. customto quench
  5. customthe reaction
  6. extractionThe reaction mixture was extracted with ethyl acetate
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio)

Sources & evidence

ORD record
ord-a01f4add24304e71a9b1296edab17eb3
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

Loading…