Buchwald–Hartwig amination: N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide → 2-Cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide
13% yield, run at 80 °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 | N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide | C₁₅H₂₀BrNO | |
| Reactant | Morpholine | C₄H₉NO | |
| Reagent | potassium 2-methylpropan-2-olate | C₄H₉KO | |
| Catalyst | 2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl | C₂₆H₃₆NP | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 2-Cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide | C₁₉H₂₈N₂O₂ | 13.21% |
Conditions
- Temperature
- 80 °C
Yield
- 13% of 2-Cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide.
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-(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%
Procedure
Copied from the source record, unedited
Exemplar cmpd from, though employing slightly different Buchwald-Hartwig coupling conditions. Tris(dibenzylidenacetone)dipalladium(0) (31 mg, 0.03 mmol) and 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (27 mg, 0.07 mmol) were stirred in anhydrous toluene (3 mL) for 15 minutes under an argon (g) sparge. To the stirring soluntion was added the N-(4-bromo-2,6-dimethylphenyl)-2-cyclopentylacetamide (208 mg, 0.67 mmol) and morpholine (0.070 mL, 0.80 mmol) neat, followed by the potassium tert-butoxide (1M in THF) (0.94 mL, 0.94 mmol) via syringe. he mixture was then heated in a sealed vessel to 80 °C for 18hrs before cooling to ambint temperature. The mixture was filtered thru a 0.7uM GMF. The resultant crude solution was subject to flash chromatorgraphy (SiO2 \- 12 g; gradient eluti
The source
This record comes from experimental reaction archive (ord-25b2f8bfafe540368db659a4bd1935bf). Open the source and check it against what is on this page.
experimental reaction archive record ord-25b2f8bfafe540368db659a4bd1935bf 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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