7-iodo-6-methoxybenzofuran-3(2H)-one → Tert-butyl 4-[4-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)but-3-ynyl]piperazine-1-carboxylate

HRID 1749951Notes

Reaction equation

HRID 1749951 reaction equation
[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)[CH2:2][C:3]#[CH:4].I[C:19]1[C:27]2[O:26][CH2:25][C:24](=[O:28])[C:23]=2[CH:22]=[CH:21][C:20]=1[O:29][CH3:30]>C(N(CC)CC)C.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.[Cu]I>[CH3:30][O:29][C:20]1[CH:21]=[CH:22][C:23]2[C:24](=[O:28])[CH2:25][O:26][C:27]=2[C:19]=1[C:4]#[C:3][CH2:2][CH2:1][N:5]1[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]1

Participants

6

Reactant 2

HCID 712788737-iodo-6-methoxybenzofuran-3(2H)-oneHCID 72213388Tert-butyl 4-(but-3-yn-1-yl)piperazine-1-carboxylate

Product 1

HCID 71278868Tert-butyl 4-[4-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)but-3-ynyl]piperazine-1-carboxylateYield 35.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A solution of tert-butyl 4-(but-3-ynyl)piperazine-1-carboxylate (0.316 g, 1.33 mmol) in triethylamine (5 mL) was added with 7-iodo-6-methoxybenzofuran-3(2H)-one (0.385 g, 1.33 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.0933 g, 0.133 mmol) and copper(I) iodide (0.0127 g, 0.0665 mmol), and the mixture was stirred at 50° C. for 4 hours. The reaction mixture was concentrated, and then added with water, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain tert-butyl 4-[4-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)but-3-ynyl]piperazine-1-carboxylate (0.189 g, 35%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionadded with water
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-bb99479f8632433f9baa49d43d729fbf
Source dataset
uspto-grants-2015_10
Patent number
US09156827B2

Reaction notes

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