Tetrahydrofuran → tert-Butyl [3-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)phenyl]carbamate

HRID 541895

Reaction equation

HRID 541895 reaction equation
I[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].O1CCCC1.[C:24]([C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:29]=[CH:30][CH:31]=1)#[CH:25]>[Cu]I.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.C(N(CC)CC)C>[C:14]([O:13][C:12]([NH:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:25]#[C:24][C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH:29]=[CH:30][CH:31]=1)=[O:18])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 7098713Tert-butyl 4-nitro-2-iodophenylcarbamateHCID 11275982tert-Butyl 3-ethynylphenylcarbamate

Product 1

HCID 57962078tert-Butyl [3-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)phenyl]carbamateYield 80%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
65 °C

Procedure

Into the reaction flask was added tert-butyl (2-iodo-4-nitrophenyl)carbamate (2.71 g, 7.44 mmol), copper(I) iodide (0.057 g, 0.30 mmol), bis(triphenylphosphine)palladium(II) chloride (0.21 g, 0.30 mmol), tetrahydrofuran (20 mL), and triethylamine (1.1 mL). It was stirred under N2 bubbling for 5 min. tert-Butyl (3-ethynylphenyl)carbamate (1.62 g, 7.44 mmol) was then added. The reaction mixture was stirred at 65° C. for 3 h. After concentration, the residue was diluted with EtOAc and water. The aqueous layer was extracted again with fresh EtOAc. The organic layers were combined and dried over Na2SO4. After filtration and concentration, the crude was purified by silica gel column chromatography to give the desired product (2.7 g, 80%). LCMS for C24H28N3O6 (M+H)+: m/z=454.1.

Workup

  1. additionwas then added
  2. concentrationAfter concentration
  3. additionthe residue was diluted with EtOAc and water
  4. extractionThe aqueous layer was extracted again with fresh EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe crude was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c82fa81207d14310b0474358618309e4
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Linked notes

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