Buchwald–Hartwig amination: Benzene, 4-bromo-1,2-dimethoxy- → tert-butyl (2R)-4-(3,4-dimethoxyphenyl)-2-propan-2-ylpiperazine-1-carboxylate
91% yield, run at 150 °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 | Benzene, 4-bromo-1,2-dimethoxy- | C₈H₉BrO₂ | |
| Reactant | (R)-1-Boc-2-isopropylpiperazine | C₁₂H₂₄N₂O₂ | |
| 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 | tert-butyl (2R)-4-(3,4-dimethoxyphenyl)-2-propan-2-ylpiperazine-1-carboxylate | C₂₀H₃₂N₂O₄ | 90.52% |
Conditions
- Temperature
- 150 °C
Yield
- 91% of tert-butyl (2R)-4-(3,4-dimethoxyphenyl)-2-propan-2-ylpiperazine-1-carboxylate.
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 |
|---|---|---|---|---|---|
| Tris(1,1-dimethylethyl)phosphine; Bis(tri-tert-butylphosphine)palladium(0) | potassium 2-methylpropan-2-olate | Tetrahydrofuran | 150 °C | — | 91% (this run) |
| 2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 150 °C | — | 60% |
Procedure
Copied from the source record, unedited
22-Apr-09 09:56:23 +0100 4-bromo-1,2-dimethoxybenzene (0.068 mL, 0.46 mmol), (R)-tert-butyl 2-isopropylpiperazine-1-carboxylate (126 mg, 0.55 mmol) and BIS(TRI-T- BUTYLPHOSPHINE)PALLADIUM(0) (23.54 mg, 0.05 mmol) and potassium 2-methylpropan-2-olate (76 mg, 0.64 mmol) were suspended in THF (5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. LC-MS shows no starting material. The reaction mixture was filtered and the crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(3,4-dimethoxyphenyl)-2-isopropylpiperazine-1-carboxylate (152 mg, 91 %) as a yellow gum.
The source
This record comes from experimental reaction archive (ord-dcac8bcfa5124a8baee8e28e5e992678). Open the source and check it against what is on this page.
experimental reaction archive record ord-dcac8bcfa5124a8baee8e28e5e992678 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.
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