Buchwald–Hartwig amination: Ethyl 4-bromobenzofuran-2-carboxylate → Ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate
27% yield, run at 95 °C, as recorded by experimental reaction archive. The written procedure is below. One of 3 recorded runs making this product; all of them are compared below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | Ethyl 4-bromobenzofuran-2-carboxylate | C₁₁H₉BrO₃ | |
| Reactant | 1-Benzylpiperazine | C₁₁H₁₆N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | Ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate | C₂₂H₂₄N₂O₃ | 26.58% |
Conditions
- Temperature
- 95 °C
Yield
- 27% of Ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate.
Every recorded run making this product
3 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 95 °C | — | 27% (this run) |
| 2-(Di-tert-butylphosphino)biphenyl; Bis(dibenzylideneacetone)palladium | Cesium carbonate | Toluene | 100 °C | — | 0% |
| Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | potassium 2-methylpropan-2-olate | Toluene | 50 °C | — | 0% |
Procedure
Copied from the source record, unedited
ethyl 4-bromobenzofuran-2-carboxylate (1 g, 3.72 mmol), 1-Benzylpiperazine (0.580 mL, 3.34 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.170 g, 0.19 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.177 g, 0.37 mmol) and CESIUM CARBONATE (1.574 g, 4.83 mmol) in dioxane (5 mL) were heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate (0.360 g, 26.6 %). MS (
The source
This record comes from experimental reaction archive (ord-c63ae2b686b74eaaae695094af43fe92). Open the source and check it against what is on this page.
experimental reaction archive record ord-c63ae2b686b74eaaae695094af43fe92 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.
How to read this record
This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.
The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.
Where to next
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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