Buchwald–Hartwig amination: Bromobenzene → (4-Cyclobutylpiperazin-1-yl)-(7-phenyl-7-azaspiro[3.5]nonan-2-yl)methanone
47% 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 | Bromobenzene | C₆H₅Br | |
| Reactant | 7-Azaspiro[3.5]nonan-2-yl-(4-cyclobutylpiperazin-1-yl)methanone | C₁₇H₂₉N₃O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | (4-Cyclobutylpiperazin-1-yl)-(7-phenyl-7-azaspiro[3.5]nonan-2-yl)methanone | C₂₃H₃₃N₃O | 46.78% |
Conditions
- Temperature
- 110 °C
Yield
- 47% of (4-Cyclobutylpiperazin-1-yl)-(7-phenyl-7-azaspiro[3.5]nonan-2-yl)methanone.
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.
- Diphenylpyrrolidine90%
- (4-Cyclobutylpiperazin-1-yl)-(7-pyridin-2-yl-7-azaspiro[3.5]nonan-2-yl)methanone43%
- n-Phenylsulfanilamide30%
- 1,2-Diphenylpiperidine16%
- (3-(Phenylamino)phenyl)methanol11%
- (4-Cyclobutylpiperazin-1-yl)-(7-pyridin-3-yl-7-azaspiro[3.5]nonan-2-yl)methanone8%
- tert-butyl N-[2-(1-phenylpiperidin-4-yl)ethyl]carbamate0%
Procedure
Copied from the source record, unedited
cesium carbonate (123 mg, 0.38 mmol) was added to a solution of (4-cyclobutylpiperazin-1-yl)(7-azaspiro[3.5]nonan-2-yl)methanone (100 mg, 0.34 mmol), PdOAc2 (7.70 mg, 0.03 mmol), BINAP (42.7 mg, 0.07 mmol) and bromobenzene (56.6 mg, 0.36 mmol) in toluene (5 mL). The reaction mixture was heated to 110°C for 18hrs. The room temperature cooled down mixture was filtered over celite. The solvent was concentrated. The product was purified by preparative HPLC using a low pH shallow gradient method (Mobile phase: 20-40% B; A: H2O with 0.05% TFA , B: CH3CN, 25 min. run) on Luna 15 m, C8 (2), 21.2x250 mm Phenomenex reverse phase column to provide (4-cyclobutylpiperazin-1-yl)(7-phenyl-7-azaspiro[3.5]nonan-2-yl)methanone (59.0 mg, 46.8 %) as white solid. 1H NMR (400 MHz, CHLOROFORM- _d_ ) d ppm 1.60
The source
This record comes from experimental reaction archive (ord-2bde997c68344c96991dffb75b1f4b33). Open the source and check it against what is on this page.
experimental reaction archive record ord-2bde997c68344c96991dffb75b1f4b33 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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