Buchwald–Hartwig amination: 1-Bromo-4-iodobenzene → 1-(4-Bromophenyl)-cis-3,5-dimethylpiperazine
62% yield, run at 90 °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-Bromo-4-iodobenzene | C₆H₄BrI | |
| Reactant | rel-(2R,6S)-2,6-dimethylpiperazine | C₆H₁₄N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 1-(4-Bromophenyl)-cis-3,5-dimethylpiperazine | C₁₂H₁₇BrN₂ | 61.61% |
Conditions
- Temperature
- 90 °C
Yield
- 62% of 1-(4-Bromophenyl)-cis-3,5-dimethylpiperazine.
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.
Procedure
Copied from the source record, unedited
sodium 2-methylpropan-2-olate (4.08 g, 42.42 mmol) was added to (2R,6S)-2,6-dimethylpiperazine (4.84 g, 42.42 mmol) in dioxane (300 mL) at 21°C under nitrogen. Stirred for 5 mins. 1-bromo-4-iodobenzene (8 g, 28.28 mmol) added, followed by diacetoxypalladium (0.635 g, 2.83 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.27 g, 5.66 mmol). Reaction evacuated and refilled with nitrogen several times. Heated at 90C for 18hours. Diluted with ethyl acetate and filtered through celite. The organic layer was washed with water ( 500ml) and then dried over Na2SO4, filtered and reduced in volume. Filtered - lcms messy. Dissolved in DCM and combined with the filtrate - adsorbed onto silica. The crude product was purified by flash silica chromatography, elution gradient 0 to 30%
The source
This record comes from experimental reaction archive (ord-76b900b67381471d89fef9247f442cb0). Open the source and check it against what is on this page.
experimental reaction archive record ord-76b900b67381471d89fef9247f442cb0 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.
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Where to next
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