Buchwald–Hartwig amination: 1-Fluoro-2-iodo-4-(trifluoromethyl)benzene → 5-bromo-N-[2-fluoro-5-(trifluoromethyl)phenyl]-4-methoxypyrimidin-2-amine
81% 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 | 1-Fluoro-2-iodo-4-(trifluoromethyl)benzene | C₇H₃F₄I | |
| Reactant | 2-Amino-5-bromo-4-methoxypyrimidine | C₅H₆BrN₃O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| 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 | 5-bromo-N-[2-fluoro-5-(trifluoromethyl)phenyl]-4-methoxypyrimidin-2-amine | C₁₂H₈BrF₄N₃O | 80.85% |
Conditions
- Temperature
- 100 °C
Yield
- 81% of 5-bromo-N-[2-fluoro-5-(trifluoromethyl)phenyl]-4-methoxypyrimidin-2-amine.
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 | Cesium carbonate | Toluene | 100 °C | — | 81% (this run) |
| Tris(furan-2-yl)phosphane; Palladium (II) acetate | Cesium carbonate | Toluene | 90 °C | — | 0% |
Procedure
Copied from the source record, unedited
To a microwave vial was added a mixture of 5-bromo-4-methoxypyrimidin-2-amine (0.570 g, 2.79 mmol), diacetoxypalladium (0.059 g, 0.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152.9 mg, 0.26 mmol), 1-fluoro-2-iodo-4-(trifluoromethyl)benzene (0.99 g, 3.41 mmol) and toluene (17 mL) under inert atmosphare. The reaction mixture was sealed and heated at 100 °C under 16h. The LCMS indicated a complete conversion of the SM. The reaction mixture was partitioned between ethyl acetate and aqueous NH4Cl- solution. The organic layer was washed with NH4Cl-solution, brine dried over sodium sulphate, filtered and concentrated in vacuum to give a yellow gum. The oil dissolved in dichloromethane charged on silica 100g and purified by flash chromatography eluting with Ethyl acet
The source
This record comes from experimental reaction archive (ord-49d889221a9546a98e62a35726966f57). Open the source and check it against what is on this page.
experimental reaction archive record ord-49d889221a9546a98e62a35726966f57 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.
Open in the Reaction Lab
The atom map, the bonds that break and form, and records running the same transformation.
Percent yield calculator
Work out a yield from what you isolated against what the equation allows.
Molecules A–Z
Every named molecule, with its identifiers and sources.