Buchwald–Hartwig amination: 2-Bromopyridine → (4-Cyclobutyl-piperazin-1-yl)-(6-pyridin-2-yl-6-aza-spiro[2.5]oct-1-yl)-methanone
27% yield, run at 160 °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 | 2-Bromopyridine | C₅H₄BrN | |
| Reactant | (6-Aza-spiro[2.5]oct-1-yl)-(4-cyclobutyl-piperazin-1-yl)-methanone | C₁₆H₂₇N₃O | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | (4-Cyclobutyl-piperazin-1-yl)-(6-pyridin-2-yl-6-aza-spiro[2.5]oct-1-yl)-methanone | C₂₁H₃₀N₄O | 26.61% |
Conditions
- Temperature
- 160 °C
Yield
- 27% of (4-Cyclobutyl-piperazin-1-yl)-(6-pyridin-2-yl-6-aza-spiro[2.5]oct-1-yl)-methanone.
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.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Palladium (II) acetate | sodium 2-methylpropan-2-olate | Toluene | 160 °C | — | 27% (this run) |
| 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Palladium (II) acetate | sodium 2-methylpropan-2-olate | 160 °C | — | 9% |
Procedure
Copied from the source record, unedited
(4-cyclobutylpiperazin-1-yl)(6-azaspiro[2.5]octan-1-yl)methanone (100 mg, 0.36 mmol), Sodium tert-butoxide (34.6 mg, 0.36 mmol) and 2-bromopyridine (62.7 mg, 0.40 mmol) were weighted in a microwave vial. A solution of Palladium(II) acetate (4.05 mg, 0.02 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (X-Phos) (8.59 mg, 0.02 mmol) in toluene (3.75 mL) and tert-butanol (0.75 mL)was added and the mixture heated at 160 °C for 10 minutes, and then 20 minutes more. The mixture was evaporated to dryness, redissolved in a minimum of methanol, filtered and purified on preparative HPLC using the long high pH (acetonitrile in water ammonium carbonate buffer, 25 min.) 20 to 40% gradient method on XBridge Prep C18 OBD, 30x150 mm, 5 mm, Waters reverse phase column, giving (4-cyclobu
The source
This record comes from experimental reaction archive (ord-dd547470ed614a60b02e180b7f0d2acd). Open the source and check it against what is on this page.
experimental reaction archive record ord-dd547470ed614a60b02e180b7f0d2acd 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.
Open in the Reaction Lab
The atom map, the bonds that break and form, and records running the same transformation.
Percent yield calculator
Work out a yield from what you isolated against what the equation allows.
Molecules A–Z
Every named molecule, with its identifiers and sources.