Buchwald–Hartwig amination: 1-Bromo-4-phenylmethoxybenzene → (R)-4-(4-benzyloxyphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester
36% yield, run at 150 °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-phenylmethoxybenzene | C₁₃H₁₁BrO | |
| Reactant | (R)-1-Boc-3-methylpiperazine | C₁₀H₂₀N₂O₂ | |
| Reagent | potassium 2-methylpropan-2-olate | C₄H₉KO | |
| Catalyst | Tris(1,1-dimethylethyl)phosphine | C₁₂H₂₇P | |
| Catalyst | Bis(tri-tert-butylphosphine)palladium(0) | C₂₄H₅₄P₂Pd | |
| Solvent | Tetrahydrofuran | C₄H₈O | |
| Product | (R)-4-(4-benzyloxyphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester | C₂₃H₃₀N₂O₃ | 35.73% |
Conditions
- Temperature
- 150 °C
Yield
- 36% of (R)-4-(4-benzyloxyphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester.
Procedure
Copied from the source record, unedited
A mixture of 1-(benzyloxy)-4-bromobenzene (158 mg, 0.60 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (60.1 mg, 0.3 mmol), bis(tri-t- butylphosphine)palladium(0) (15.33 mg, 0.03 mmol) and potassium tert-butoxide (37.0 mg, 0.33 mmol) in THF (2 mL) was flushed with nitrogen and sealed into a microwave tube. The reaction was heated to 150 °C for 20 minutes in the microwave reactor and cooled to RT. The reaction mixture was filtered and the filtrate evaporated to dryness. The residue was dissolved in MeOH (5mL) and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in
The source
This record comes from experimental reaction archive (ord-8459652e6963448495d966b232514570). Open the source and check it against what is on this page.
experimental reaction archive record ord-8459652e6963448495d966b232514570 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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