Piperidine → HCID 22481762, compound

HRID 2181659Notes

Reaction equation

HRID 2181659 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1I.[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.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[C:17]1[O:1][C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[CH:18]=1)[CH3:14]

Participants

7

Reactant 3

HCID 8082PiperidineHCID 20858Propane, 1,1-diethoxy-HCID 11346465Methyl 4-hydroxy-3-iodobenzoate

Product 1

HCID 22481762HCID 22481762, compoundYield 53.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 4-hydroxy-3-iodo-benzoate (9.9 g, 35 mmol) is combined with propioaldehyde diethylacetal (5.6 ml, 39 mmol), bis(triphenylphosphine)palladium(II) chloride (523 mg, 0.7 mmol), cuprous iodide (266 mg, 1.4 mmol), and piperidine (3.9 ml, 39 mmol) in DMF (50 ml) in a dry flask under nitrogen. The reaction is warmed to 60° C. for 6 h and is stirred overnight at RT. The mixture is diluted with EtOAc (250 ml) and is washed with 2:1:1:0.1 water/brine/saturated NaHCO3/conc. NH4OH (4×100 ml). The organic layer is dried (MgSO4) and is concentrated in vacuo to a dark oil. The crude material is chromatographed over 300 g silica gel (230-400 mesh), eluting with 15% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 5.2 g (48%) methyl 2-(diethoxymethyl)-1-benzofuran-5-carboxylate as an amber oil. HRMS (EI) calcd for C15H18O5: 278.1154, found 278.1156 (M)+.

Workup

  1. washis washed with 2:1:1:0.1 water/brine/saturated NaHCO3/conc
  2. dry with materialThe organic layer is dried (MgSO4)
  3. concentrationis concentrated in vacuo to a dark oil
  4. customThe crude material is chromatographed over 300 g silica gel (230-400 mesh)
  5. washeluting with 15% EtOAc/hexane
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9951192065a64a879b51c98fad56f28f
Source dataset
uspto-grants-2005_05
Patent number
US06894042B2

Reaction notes

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