Propyne → Methyl 3-prop-1-ynyl-1-benzofuran-5-carboxylate

HRID 2181686Notes

Reaction equation

HRID 2181686 reaction equation
Br[C:2]1[C:6]2[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:5]=2[O:4][CH:3]=1.[C:15](P(C(C)(C)C)C(C)(C)C)(C)([CH3:17])[CH3:16].C#CC>O1CCOCC1.CCOC(C)=O.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[C:16]([C:2]1[C:6]2[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:5]=2[O:4][CH:3]=1)#[C:15][CH3:17]

Participants

7

Reactant 3

HCID 6335PropyneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 22481688Methyl 3-bromo-1-benzofuran-5-carboxylate

Product 1

HCID 22481806Methyl 3-prop-1-ynyl-1-benzofuran-5-carboxylateYield 226%

Reagents, catalysts & solvents 3

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 3-bromobenzofuran-5-carboxylate (750 mg, 2.94 mmol) is combined with bis(benzonitrile)palladium dichloride (169 mg, 0.44 mmol), cuprous iodide (19 mg, 0.10 mmol), tri-t-butylphosphine ((10% in hexane) 1.92 ml, 0.95 mmol), and propyne (2 ml, 35 mmol) in 7 ml dry dioxane in 15 ml screw cap pressure tube under nitrogen. The mixture is treated with DIA (494 μL, 3.6 mmol), is stirred overnight at RT, and is diluted with 50 ml EtOAc. The reaction is washed with 4×25 ml 1:1:0.1 H2O/brine/conc. NH4OH, the organic layer is dried (MgSO4), and the volatiles are removed in vacuo. The crude material is chromatographed over 50 g silica gel (230-400 mesh) eluting with 12% EtOAc/hexane. The appropriate fractions are combined and concentrated to give 460 mg (73%) of methyl 3-prop-1-ynyl-1-benzofuran-5-carboxylate as a pale solid. MS for C13H10O3 (EI) m/z (rel. intensity): 214 (M)+.

Workup

  1. customscrew cap pressure tube under nitrogen
  2. additionThe mixture is treated with DIA (494 μL, 3.6 mmol)
  3. washThe reaction is washed with 4×25 ml 1:1:0.1 H2O/brine/conc
  4. dry with materialNH4OH, the organic layer is dried (MgSO4)
  5. customthe volatiles are removed in vacuo
  6. customThe crude material is chromatographed over 50 g silica gel (230-400 mesh)
  7. washeluting with 12% EtOAc/hexane
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ee0a4f95dac3458ca4743e8deb71f3d8
Source dataset
uspto-grants-2005_05
Patent number
US06894042B2

Reaction notes

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