3-Ethynylbenzoic acid methyl ester → Methyl 3-((4-(2-acetamidopropyl)phenyl)ethynyl)benzoate

HRID 76177Notes

Reaction equation

HRID 76177 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])#[CH:2].I[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH:21]([NH:23][C:24](=[O:26])[CH3:25])[CH3:22])=[CH:16][CH:15]=1>CN(C=O)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[C:24]([NH:23][CH:21]([CH3:22])[CH2:20][C:17]1[CH:18]=[CH:19][C:14]([C:2]#[C:1][C:3]2[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=2)[C:6]([O:8][CH3:9])=[O:7])=[CH:15][CH:16]=1)(=[O:26])[CH3:25]

Participants

6

Reactant 2

HCID 112751593-Ethynylbenzoic acid methyl esterHCID 66611344N-(1-(4-Iodophenyl)propan-2-YL)acetamide

Product 1

HCID 66611163Methyl 3-((4-(2-acetamidopropyl)phenyl)ethynyl)benzoate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To 10.0 g (63.4 mmol) methyl 3-ethynylbenzoate (J. Org. Chem. 1981, 46, 2280-6) and 7.00 g (23.1 mmol) N-(1-(4-iodo-phenyl)propan-2-yl)acetamide (I52.1) in 80 mL DMF are added 100 mL TEA, 250 mg (1.31 mmol) CuI and 1.20 g (1.71 mmol) bis(triphenylphosphine)-palladium (II) chloride. After stirring over night r.t. the solvents are removed under reduced pressure. The residue is partitioned between EtOAc and diluted aq. NH4Cl solution. The organic layer is separated and the aq. layer is extracted with EtOAc (2×). The org. layers are combined, washed with brine, dried with Na2SO4 and the solvent is removed in vacuo. The residue is purified by column chromatography (silica gel, EtOAc 100%).

Workup

  1. customare removed under reduced pressure
  2. customThe residue is partitioned between EtOAc and diluted aq. NH4Cl solution
  3. customThe organic layer is separated
  4. extractionthe aq. layer is extracted with EtOAc (2×)
  5. washwashed with brine
  6. dry with materialdried with Na2SO4
  7. customthe solvent is removed in vacuo
  8. customThe residue is purified by column chromatography (silica gel, EtOAc 100%)

Sources & evidence

ORD record
ord-80a171854e3a4cd182eb4751a6186526
Source dataset
uspto-grants-2014_09
Patent number
US08835472B2

Reaction notes

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