Buchwald–Hartwig amination: 2-Bromo-5-fluorobenzotrifluoride → (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine
59% yield, run at 100 °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-fluorobenzotrifluoride | C₇H₃BrF₄ | |
| Reactant | 2-Methylpiperazine, (R)- | C₅H₁₂N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine | C₁₂H₁₄F₄N₂ | 59% |
Conditions
- Temperature
- 100 °C
Yield
- 59% of (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine.
Procedure
Copied from the source record, unedited
1-bromo-4-fluoro-2-(trifluoromethyl)benzene (5 g, 20.58 mmol), (R)-2-methylpiperazine (2.164 g, 21.61 mmol), sodium tert-butoxide (3.95 g, 41.15 mmol) and BINAP (0.512 g, 0.82 mmol) in anhydrous toluene (60 mL) was degassed under vacuum with inlet of nitrogen. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.377 g, 0.41 mmol) was added, the mixture again degassed. The resulting suspension was stirred at 100 °C for 6 hours under nitrogen. LCMS: Product formed. Cooled and evaporated. Residue diluted with diethyl ether (75 mL), filtered through Celite and the filtrates extracted with 2M HCl (2x30 mL). The combined aqueous layers were basified with solid NaOH to pH ~10, extracted with diethyl ether (2x50 mL), the organic extracts washed with water (2x10 mL) and brine, dried over mgSO4, filtered a
The source
This record comes from experimental reaction archive (ord-5ffc5c4a730b4c9fa67430c9657da268). Open the source and check it against what is on this page.
experimental reaction archive record ord-5ffc5c4a730b4c9fa67430c9657da268 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
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