Buchwald–Hartwig amination: 3-Iodobenzyloxybenzene → 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole
10% 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 | Toluene | C₇H₈ | |
| Product | 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole | C₂₃H₁₈F₃NO₂ | 10.45% |
Conditions
- Temperature
- 120 °C
Yield
- 10% 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% |
| 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% (this run) |
Procedure
Copied from the source record, unedited
EN04773-52, _Buchwald coupling, toluene and iodide_ The indole from 4773-25, 1-(benzyloxy)-3-iodobenzene,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and 50% conversion was observed on NMR*(see attached NMR). The mixture was warmed further 15h at 120°C, still starting material left but the reaction mixture was directly applied to a silica column (heptane 3:1). Product was collected in fraction 22-23 (see attached NMR). Only 19.3 mg (10.45% yield) could be collected but NMR showed correct product. Test reaction with bromide was performed in 4773-53. ######################### *Small amount from reaction mixture was dissolved in CDCl3 and 1HNMR analysis was performed)
The source
This record comes from experimental reaction archive (ord-055c0d9926684c29963cad751105f26e). Open the source and check it against what is on this page.
experimental reaction archive record ord-055c0d9926684c29963cad751105f26e 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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More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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