Buchwald–Hartwig amination: 1,4-Dibromobenzene → Ethyl 1-(4-bromophenyl)piperidine-4-carboxylate
59% yield, run at 85 °C, as recorded by experimental reaction archive. The written procedure is below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 1,4-Dibromobenzene | C₆H₄Br₂ | |
| Reactant | Ethyl 4-piperidinecarboxylate | C₈H₁₅NO₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | Ethyl 1-(4-bromophenyl)piperidine-4-carboxylate | C₁₄H₁₈BrNO₂ | 59.1% |
Conditions
- Temperature
- 85 °C
Yield
- 59% of Ethyl 1-(4-bromophenyl)piperidine-4-carboxylate.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
- 1-(4-Bromophenyl)-3-methylazetidine85%
- Methyl 1-(4-bromophenyl)pyrrolidine-3-carboxylate32%
- Methyl 2-(4-(4-bromophenyl)piperazin-1-yl)acetate0%
- Ethyl 1-(6-chloro-4-methyl-3-pyridinyl)piperidine-4-carboxylate0%
- Ethyl 1-(4-(tert-butoxycarbonyl)phenyl)piperidine-4-carboxylate0%
- Ethyl 1-(6-chloro-4-methyl-3-pyridinyl)piperidine-4-carboxylate0%
Procedure
Copied from the source record, unedited
A suspension of ethyl piperidine-4-carboxylate (3.27 mL, 21.20 mmol), 1,4-dibromobenzene (5 g, 21.20 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.485 g, 0.53 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.990 g, 1.59 mmol) and Sodium Tert-Butoxide (2.444 g, 25.43 mmol) in anhydrous toluene (60 mL) was stirred at 85 °C under nitrogen for 16 hours. The reaction was cooled to ambient temperature, diluted with Ether (100 mL) and filtered through celite. The filtrate was evaporated in vacuo to yield crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Pure fractions were evaporated to dryness to afford ethyl 1-(4-bromophenyl)piperidine-4-carboxylate (3.91 g, 59.1 %) as a yellow oil.
The source
This record comes from experimental reaction archive (ord-6d4c20d55c834a949848dd34c3fa431d). Open the source and check it against what is on this page.
experimental reaction archive record ord-6d4c20d55c834a949848dd34c3fa431d 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
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