Buchwald–Hartwig amination, record ord-c1f0d60afc5d442f82c1963456675035
One recorded run of this reaction. Below is what the source recorded, and nothing added to it.
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 1-Bromo-3,5-difluorobenzene | C₆H₃BrF₂ | |
| Reactant | N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide | C₂₀H₂₅N₃O₄ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Br[Pd+].CC1(C)c2cccc([PH+](c3ccccc3)c3ccccc3)c2Oc2c([PH+](c3ccccc3)c3ccccc3)cccc21.Fc1c[c-]cc(F)c1 | C₄₅H₃₇BrF₂OP₂Pd+2 | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide | C₂₆H₂₇F₂N₃O₄ | 33.8% |
Conditions
- Temperature
- 80 °C
Yield
- 34% of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide.
Procedure
Copied from the source record, unedited
Pd complexe (2.96 mg, 3.37 µmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (25 mg, 0.07 mmol), 1-bromo-3,5-difluorobenzene (8.53 µl, 0.07 mmol) and cesium carbonate (32.9 mg, 0.10 mmol) dissolved in 1,4-dioxane (0.5 ml) under argon. The resulting suspension was degased with argon and then stirred at 80 °C for 3.5 hours. Lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to
The source
This record comes from experimental reaction archive (ord-c1f0d60afc5d442f82c1963456675035). Open the source and check it against what is on this page.
experimental reaction archive record ord-c1f0d60afc5d442f82c1963456675035 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.