Buchwald–Hartwig amination: 4-Bromophenol → 4-Morpholinophenol
31% 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 | 4-Bromophenol | C₆H₅BrO | |
| Reactant | Morpholine | C₄H₉NO | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 4-Morpholinophenol | C₁₀H₁₃NO₂ | 31.25% |
Conditions
- Temperature
- 100 °C
Yield
- 31% of 4-Morpholinophenol.
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-(6-Bromopyridin-3-yl)morpholine56%
- 4-(4-Methyl-1-piperazinyl)phenol51%
- 4-(5-Bromopyridin-3-yl)morpholine50%
- Methyl 3-bromo-4-morpholinobenzoate32%
- 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%
Procedure
Copied from the source record, unedited
4-Bromophenol (865 mg, 5 mmol), Tris(dibenzylideneacetone)dipalladium(0) (229 mg, 0.25 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (238 mg, 0.50 mmol), Morpholine (0.437 mL, 5.00 mmol) and sodium tert-butoxide (1009 mg, 10.50 mmol) were stirred in toluene (5 mL) overnight at 100 °C. The mixture was allowed to cool to ambient temperature. Ethylacetate was added and the mixture was washed with aqueous NaHCO3 (satd.) and water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-2 % MeOH in DCM. The collected fraction were combined and the solvent was removed by rotary evaporation. 1H NMR in CDCl3 is consistent with desired product MS (m+1)
The source
This record comes from experimental reaction archive (ord-c3c3446fa521406ab3b5349b3ab1378a). Open the source and check it against what is on this page.
experimental reaction archive record ord-c3c3446fa521406ab3b5349b3ab1378a 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.
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