Buchwald–Hartwig amination: 1-Bromo-3,5-difluorobenzene → methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate
40% 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-Bromo-3,5-difluorobenzene | C₆H₃BrF₂ | |
| Reactant | methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate | C₁₉H₂₂N₂O₅ | |
| 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 | methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate | C₂₅H₂₄F₂N₂O₅ | 39.87% |
Conditions
- Temperature
- 100 °C
Yield
- 40% of methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate.
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 | 1,4-Dioxane | 100 °C | — | 66% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); C45H37BrF2OP2Pd+2 | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 40% (this run) |
Procedure
Copied from the source record, unedited
Pd complexe (147 mg, 0.17 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (600 mg, 1.67 mmol), 1-bromo-3,5-difluorobenzene (0.241 ml, 2.09 mmol) and cesium carbonate (818 mg, 2.51 mmol) dissolved in 1,4-dioxane (12 ml). The resulting suspension was degased with argon and then stirred at 100 °C (15:00) for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (314 mg, 39.9 %) as a clear yellow solid.
The source
This record comes from experimental reaction archive (ord-d7d32d49e289422b9b8afc82aae7319c). Open the source and check it against what is on this page.
experimental reaction archive record ord-d7d32d49e289422b9b8afc82aae7319c 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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