Buchwald–Hartwig amination: 3-Iodobenzyloxybenzene → 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole
40% yield, run at 120 °C, as recorded by experimental reaction archive. The written procedure is below. One of 3 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 | 3-Iodobenzyloxybenzene | C₁₃H₁₁IO | |
| Reactant | 2-Methyl-6-(trifluoromethoxy)-1H-indole | C₁₀H₈F₃NO | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-(Di-tert-butylphosphino)biphenyl | C₂₀H₂₇P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole | C₂₃H₁₈F₃NO₂ | 40.17% |
Conditions
- Temperature
- 120 °C
Yield
- 40% of 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole.
Every recorded run making this product
3 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.
| Reactants | Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|---|
| 1-(Benzyloxy)-3-bromobenzene; 2-Methyl-6-(trifluoromethoxy)-1H-indole | 2-(Di-tert-butylphosphino)biphenyl; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 80 °C | — | 62% |
| 3-Iodobenzyloxybenzene; 2-Methyl-6-(trifluoromethoxy)-1H-indole | 2-(Di-tert-butylphosphino)biphenyl; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | 1,4-Dioxane | 120 °C | — | 40% (this run) |
| 3-Iodobenzyloxybenzene; 2-Methyl-6-(trifluoromethoxy)-1H-indole | 2-(Di-tert-butylphosphino)biphenyl; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 120 °C | — | 10% |
Procedure
Copied from the source record, unedited
EN04773-50, _Buchwald coupling,_ ** _J. Med. Chem. 2009, page 3846-3854 (changed: solvent to dioxane and bromide to iodide)._** The indole from 4773-41, 1-(benzyloxy)-3-iodobenzene, Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and ~40% conversion was observed on NMR. The reaction mixture was further heated at 80 °C for 16h and 40 h, see attached 1H-NMR for reaction progress. A comparison with 4773-51 shows that using dioxane or iodide gives a lower yield (slower reaction). Switching the solvent to toluene was explored in 4773-52. The reaction in this experiment showed that the Buchwald conditions worked. Reaction mixture was thrown away.
The source
This record comes from experimental reaction archive (ord-232b7429c3f0450bb3d4836c8a002e13). Open the source and check it against what is on this page.
experimental reaction archive record ord-232b7429c3f0450bb3d4836c8a002e13 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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Where to next
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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