Buchwald–Hartwig amination: 1-Bromo-3-fluorobenzene → Methyl 8-[1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-yl-4-oxochromene-6-carboxylate
71% yield, run at 100 °C, as recorded by experimental reaction archive. The written procedure is below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 1-Bromo-3-fluorobenzene | C₆H₄BrF | |
| 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 | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | Methyl 8-[1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-yl-4-oxochromene-6-carboxylate | C₂₅H₂₅FN₂O₅ | 70.85% |
Conditions
- Temperature
- 100 °C
Yield
- 71% of Methyl 8-[1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-yl-4-oxochromene-6-carboxylate.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
Procedure
Copied from the source record, unedited
diacetoxypalladium (0.045 g, 0.20 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol), methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol) and cesium carbonate (2.455 g, 7.53 mmol) dissolved in 1,4-dioxane (35 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 11 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 20% methanol in ethyl acetate (on 50 min). The solvent was evaporated to dryness to afford methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1.610 g, 70.8 %) a
The source
This record comes from experimental reaction archive (ord-5211120ee16b4ae79338b46c711839b3). Open the source and check it against what is on this page.
experimental reaction archive record ord-5211120ee16b4ae79338b46c711839b3 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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