Buchwald–Hartwig amination: 2-Bromo-5-fluorotoluene → Tert-butyl 4-(4-fluoro-2-methylphenyl)piperazine-1-carboxylate
16% yield, run at 110 °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 | 2-Bromo-5-fluorotoluene | C₇H₆BrF | |
| Reactant | tert-Butyl piperazine-1-carboxylate | C₉H₁₈N₂O₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | Tert-butyl 4-(4-fluoro-2-methylphenyl)piperazine-1-carboxylate | C₁₆H₂₃FN₂O₂ | 16.05% |
Conditions
- Temperature
- 110 °C
Yield
- 16% of Tert-butyl 4-(4-fluoro-2-methylphenyl)piperazine-1-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.
- Methyl 4-(4-Boc-1-piperazinyl)-2-chlorobenzoate91%
- Tert-butyl 4-(7-benzo[b]furanyl)piperazine-1-carboxylate84%
- Tert-butyl 4-(2-methylpyridin-3-yl)piperazine-1-carboxylate83%
- Tert-butyl 4-(4-cyanophenyl)piperazine-1-carboxylate82%
- Tert-butyl 4-(5-(benzyloxy)pyridin-2-YL)piperazine-1-carboxylate69%
- tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate64%
- Tert-butyl 4-(2-methoxyphenyl)piperazine-1-carboxylate62%
- tert-butyl 4-(2-methyl-3-oxo-1H-isoindol-5-yl)piperazine-1-carboxylate57%
- Tert-butyl 4-(4-acetylphenyl)piperazine-1-carboxylate52%
- Tert-butyl 4-(3-chloro-4-cyanophenyl)piperazine-1-carboxylate47%
- tert-Butyl 4-(quinolin-2-yl)piperazine-1-carboxylate46%
- Tert-butyl 4-[6-[(4-methylsulfonylphenyl)methoxy]-3-pyridinyl]piperazine-1-carboxylate43%
Procedure
Copied from the source record, unedited
In a 200ml flask was added 1-bromo-4-fluoro-2-methylbenzene (2 g, 10.58 mmol) and TERT-BUTYL 1-PIPERAZINECARBOXYLATE (2.365 g, 12.70 mmol), CESIUM CARBONATE (5.17 g, 15.87 mmol) , BINAP (0.791 g, 1.27 mmol) 18-CROWN-6 (0.336 g, 1.27 mmol), followed by toluene (25 ml). Degass the mixture. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.581 g, 0.63 mmol) was added. Heat at 110oC under nitrogen in an oil bath for overnight. The reaction mixture was diluted with ethyl acetate and filtered through celite. The Celite was washed with EtOAC. The EtOAC was concentrated down to give a brown oil. The crude product was purified by silica gel column(40g) and was eluted with 0% EtOAC/Hexane -50% EtOAC/Hexane. Yield: 0.5g Yellow oil.
The source
This record comes from experimental reaction archive (ord-7ef9bb9d04ab4703a01fe4c2dfba9490). Open the source and check it against what is on this page.
experimental reaction archive record ord-7ef9bb9d04ab4703a01fe4c2dfba9490 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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