Buchwald–Hartwig amination: 2-Bromo-5-iodopyridine → 4-(6-Bromopyridin-3-yl)morpholine
56% yield, run at 20 °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 | 2-Bromo-5-iodopyridine | C₅H₃BrIN | |
| Reactant | Morpholine | C₄H₉NO | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 4-(6-Bromopyridin-3-yl)morpholine | C₉H₁₁BrN₂O | 56.05% |
Conditions
- Temperature
- 20 °C
Yield
- 56% of 4-(6-Bromopyridin-3-yl)morpholine.
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.
- Dimethyl 5-morpholinoisophthalate78%
- Ethyl 4-(2-fluoro-4-methylanilino)-7-(2-methoxyethoxy)-6-morpholin-4-ylquinoline-3-carboxylate75%
- N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-3,3-dimethyl-butyramide64%
- 4-(5-Bromopyridin-3-yl)morpholine50%
- Methyl 3-bromo-4-morpholinobenzoate32%
- 4-Morpholinophenol31%
- 2,6-dimethyl-N-[(7-methyl-7-azabicyclo[2.2.1]heptan-1-yl)-(4-morpholin-4-ylphenyl)methyl]benzamide30%
- 5-Morpholin-4-yl-nicotinic acid tert-butyl ester27%
- (5-Morpholinopyridin-2-yl)methanol19%
- 2,6-dimethyl-N-[(7-methyl-7-azabicyclo[2.2.1]heptan-1-yl)-(3-morpholin-4-ylphenyl)methyl]benzamide18%
- Methyl 5-bromo-2-morpholinobenzoate18%
- 2-Cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide13%
Procedure
Copied from the source record, unedited
Pd2(dba)3 (0.564 g, 0.62 mmol) was added to 2-bromo-5-iodopyridine (5.00 g, 17.61 mmol), morpholine (1.541 mL, 17.61 mmol), sodium tert-butoxide (4.23 g, 44.03 mmol) and Xantphos (1.019 g, 1.76 mmol) in toluene (200 mL) at 20°C. The resulting solution was stirred at r.t. for 3 days (as the reaction was started on a Friday). Complete. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was dried with MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% (EtOAc:MeOH - 10:1) in heptane. Pure fractions were evaporated to dryness LCMS indicated some di-substituted product present. Triturated in heptane:EtOAc,
The source
This record comes from experimental reaction archive (ord-e0d3875cf2584a84afda6341abdff6dc). Open the source and check it against what is on this page.
experimental reaction archive record ord-e0d3875cf2584a84afda6341abdff6dc 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
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