Buchwald–Hartwig amination: 3-Bromopyridine → tert-butyl (3R)-3-methyl-4-pyridin-3-ylpiperazine-1-carboxylate
103% yield, run at 100 °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 | 3-Bromopyridine | C₅H₄BrN | |
| Reactant | (R)-1-Boc-3-methylpiperazine | C₁₀H₂₀N₂O₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl | C₃₀H₄₃O₂P | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | tert-butyl (3R)-3-methyl-4-pyridin-3-ylpiperazine-1-carboxylate | C₁₅H₂₃N₃O₂ | 102.97% |
Conditions
- Temperature
- 100 °C
Yield
- 103% of tert-butyl (3R)-3-methyl-4-pyridin-3-ylpiperazine-1-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',6'-diisopropoxybiphenyl; Palladium (II) acetate | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 103% (this run) |
| 2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl; Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 0% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 85 °C | — | 0% |
Procedure
Copied from the source record, unedited
_Repeat of reaction EN05798-78_ Diacetoxypalladium (0.112 g, 0.50 mmol) and dicyclohexyl(2',6'-diisopropoxybiphenyl-2-yl)phosphine (0.466 g, 1.00 mmol) were dissolved in toluene (15 mL) at ambient temperature under nitrogen. The mixture was degassed and purged with nitrogen several times and heated to 50°C for 20 mins. In a separate vessel, were mixed 3-bromopyridine (0.789 g, 4.99 mmol), sodium 2-methylpropan-2-olate (0.720 g, 7.49 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (1g, 4.99 mmol) and toluene (10 mL). The mixture was degassed and purged with nitrogen several times. The catalyst mixture was added to the reaction vessel and the resulting mixture was degassed and purged with nitrogen, and heated at 100 °C under nitrogen overnight. The reaction mixture was filtered th
The source
This record comes from experimental reaction archive (ord-b33a6a5e9f314a52b92d41be195f749c). Open the source and check it against what is on this page.
experimental reaction archive record ord-b33a6a5e9f314a52b92d41be195f749c 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
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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