Buchwald–Hartwig amination: 2-Bromo-4-chloropyridine → N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine
1% yield, run at 170 °C, as recorded by experimental reaction archive. The written procedure is below. One of 11 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 | 2-Bromo-4-chloropyridine | C₅H₃BrClN | |
| Reactant | 2-Aminooxazole | C₃H₄N₂O | |
| Reagent | sodium phenoxide | C₆H₅NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine | C₈H₆ClN₃O | 0.5% |
Conditions
- Temperature
- 170 °C
Yield
- 1% of N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine.
Every recorded run making this product
11 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 |
|---|---|---|---|---|---|---|
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Potassium Carbonate | Anisole | 120 °C | — | 50% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 11% |
| 2-Bromo-4-chloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 8% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Sodium hydride | 1,4-Dioxane | 140 °C | — | 3% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | sodium phenoxide | 1,4-Dioxane | 80 °C | — | 3% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 2% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | Dimethylacetamide | 100 °C | — | 2% |
| 2-Bromo-4-chloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | sodium phenoxide | 1,4-Dioxane | 170 °C | — | 1% (this run) |
| 2,4-Dichloropyridine; 2-Aminooxazole | Bis(3,5-bis(trifluoromethyl)phenyl)(3,6-dimethoxy-2',4',6'-tri(propan-2-yl)(1,1'-biphenyl)-2-yl)phosphane; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 0% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Potassium Phosphate, Tribasic | 1,4-Dioxane | 160 °C | — | 0% |
| 2,4-Dichloropyridine; 2-Aminooxazole | Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 0% |
Procedure
Copied from the source record, unedited
Objective: Improve yield of the desired product starting from the bromoaryl compound. To a flask containing 2-bromo-4-chloropyridine (196 mg, 1.02 mmol), sodium phenolate (177 mg, 1.52 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (11.63 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.64 mg, 0.03 mmol) (Xantphos), was added degassed dioxane (4 mL) and the mixture allowed to stir under nitrogen atmosphere for 5 min. To this solution was added oxazol-2-amine (94 mg, 1.12 mmol) and the reaction mixture was heated to 170 °C for 2 h under microwave irradiation. Methanol was added to the crude reaction mixture together with silica (2 g), the solvent was removed under reduced pressure and the remaining residue was placed in dry load tube prior to chromatograph
The source
This record comes from experimental reaction archive (ord-16b6dbfada904ea1b6f495fddc318fb3). Open the source and check it against what is on this page.
experimental reaction archive record ord-16b6dbfada904ea1b6f495fddc318fb3 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.
Where to next
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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