Buchwald–Hartwig amination: 5-Chloro-2-iodoanisole → 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine
64% yield, run at 100 °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 | 5-Chloro-2-iodoanisole | C₇H₆ClIO | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine | C₁₂H₁₇ClN₂O | 63.57% |
Conditions
- Temperature
- 100 °C
Yield
- 64% of 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine.
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 |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 64% (this run) |
| Binap, (A+-)-; Palladium (II) acetate | sodium 2-methylpropan-2-olate | Toluene | 80 °C | — | 0% |
Procedure
Copied from the source record, unedited
Palladium II acetate (25.09 mg, 0.11 mmol) was added to 4-chloro-1-iodo-2-methoxybenzene (300 mg, 1.12 mmol), 1-methylpiperazine (0.124 ml, 1.12 mmol), sodium 2-methylpropan-2-olate (215 mg, 2.23 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (323 mg, 0.56 mmol) in toluene (4 ml) at room temperture under nitrogen. The resulting mixture was stirred at 100oC overnight. The reaction mixture was filtered through celite and then concentrated under reduced pressure. The crude product was then taken up in DCM and washed with water. The crude product was purified by chromatography in DCM:MeOH 0-->10% to afford 1-(4-chloro-2-methoxyphenyl)-4-methylpiperazine (171 mg, 63.6 %) as yellow oil. This was carried through to the next reaction immediately as it is a controlled substance.
The source
This record comes from experimental reaction archive (ord-890c9e12800b48cca35bf6f2a67a4cca). Open the source and check it against what is on this page.
experimental reaction archive record ord-890c9e12800b48cca35bf6f2a67a4cca 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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More Buchwald–Hartwig amination records
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