Piperidine → HCID 22481729, compound

HRID 2181655Notes

Reaction equation

HRID 2181655 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1I)[C:5]([O:7][CH3:8])=[O:6].[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[CH2:17][CH3:18])[CH3:14].N1CCCCC1>CN(C=O)C.CCOC(C)=O.[Cu](I)I>[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[C:17]1[O:1][C:2]2[CH:3]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:9]=[CH:10][C:11]=2[CH:18]=1)[CH3:14]

Participants

7

Reactant 3

HCID 8082PiperidineHCID 20858Propane, 1,1-diethoxy-HCID 10378812Methyl 3-hydroxy-4-iodobenzoate

Product 1

HCID 22481729HCID 22481729, compoundYield 32.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

A dried flask under nitrogen is charged with methyl 3-hydroxy-4-iodobenzoate (10.0 g, 35.9 mmol), propioaldehyde diethyl acetal (5.72 ml, 40.0 mmol), bistriphenylphosphine palladium diacetate (538 mg, 0.72 mmol), copper iodide (273 mg, 1.4 mmol) and piperidine (3.94 ml, 40.0 mmol) in DMF (50 ml). The mixture is stirred at 45° C. for 6 h, then at RT overnight. The reaction is diluted with EtOAc (250 ml) and washed with 50% saturated 1:1 NaCl/NaHCO3 solution (4×100 ml). The organic layer is dried (Na2SO4), filtered and concentrated to a brown oil. The crude material is chromatographed over 500 g slurry-packed silica, eluting with 15% EtOAc/hexane. The appropriate fractions are collected and concentrated, affording 3.22 g (32%) of methyl 2-(diethoxymethyl)-1-benzofuran-6-carboxylate as an orange oil. 1H NMR (400 MHz, CDCl3): δ 1.29, 3.72, 3.96, 5.70, 6.88, 7.61, 7.95, 8.20 ppm.

Workup

  1. customat RT
  2. customovernight
  3. washwashed with 50% saturated 1:1 NaCl/NaHCO3 solution (4×100 ml)
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a brown oil
  7. customThe crude material is chromatographed over 500 g slurry-packed silica
  8. washeluting with 15% EtOAc/hexane
  9. customThe appropriate fractions are collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-4d3df3074ac249668a6cfe8c21477e0e
Source dataset
uspto-grants-2005_05
Patent number
US06894042B2

Reaction notes

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