Buchwald–Hartwig amination: Ethyl 4-chlorobenzofuran-2-carboxylate → tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate
64% yield, run at 95 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 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-chlorobenzofuran-2-carboxylate | C₁₁H₉ClO₃ | |
| Reactant | tert-Butyl piperazine-1-carboxylate | C₉H₁₈N₂O₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate | C₂₀H₂₆N₂O₅ | 63.8% |
Conditions
- Temperature
- 95 °C
Yield
- 64% of tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate.
Every recorded run making this product
2 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.
| Reactants | Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|---|
| Ethyl 4-chlorobenzofuran-2-carboxylate; tert-Butyl piperazine-1-carboxylate | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 95 °C | — | 64% (this run) |
| Ethyl 4-bromobenzofuran-2-carboxylate; tert-Butyl piperazine-1-carboxylate | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 95 °C | — | 45% |
Procedure
Copied from the source record, unedited
tert-butyl piperazine-1-carboxylate (5.22 g, 28.04 mmol), ethyl 4-chlorobenzofuran-2-carboxylate (6.3 g, 28.04 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (1.337 g, 2.80 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.284 g, 1.40 mmol) and CESIUM CARBONATE (11.88 g, 36.46 mmol) were heated under argon to 95 °C 14:51:42 overnight, LC showed no s.m. EN03969-25-001. The mixture was allowed to cool to rt, diluted with EtOAc (35 mL) and filtered through a pad of Celite, washed with EtOAc (total of 100 mL). The filterate was collected and the solvent was removed by rotary evaporation. The crude product was treated with diisopropylether under stirring at rt for 4 days, the mixture was filterered and washed with diisopropylether. The diisopropyletherphase was concentrat
The source
This record comes from experimental reaction archive (ord-1525568325b3443390953fb89e1c826a). Open the source and check it against what is on this page.
experimental reaction archive record ord-1525568325b3443390953fb89e1c826a 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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