tert-Butyl 4-ethynylpiperidine-1-carboxylate → Tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethynyl]piperidine-1-carboxylate

HRID 1749967Notes

Reaction equation

HRID 1749967 reaction equation
I[C:2]1[C:10]2[O:9][CH2:8][C:7](=[O:11])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:12][CH3:13].[C:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)#[CH:15]>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>[CH3:13][O:12][C:3]1[CH:4]=[CH:5][C:6]2[C:7](=[O:11])[CH2:8][O:9][C:10]=2[C:2]=1[C:15]#[C:14][CH:16]1[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]1

Participants

6

Reactant 2

HCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 712788737-iodo-6-methoxybenzofuran-3(2H)-one

Product 1

HCID 71278779Tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethynyl]piperidine-1-carboxylateYield 55%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 7-iodo-6-methoxybenzofuran-3(2H)-one (0.348 g, 1.20 mmol) synthesized in Example B46, Step 2 in triethylamine (10 mL) was added with tert-butyl 4-ethynylpiperidine-1-carboxylate (Journal of Medicinal Chemistry, Vol. 47, p. 3111, 2004, 0.276 g, 1.32 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.0842 g, 0.120 mmol) and copper(I) iodide (0.0229 g, 0.120 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethynyl]piperidine-1-carboxylate (0.245 g, 55%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-7cd12625601b43b7ada4e565599625f9
Source dataset
uspto-grants-2015_10
Patent number
US09156827B2

Reaction notes

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