Buchwald–Hartwig amination: 1,3-Benzenedicarboxylic acid, 5-bromo-, 1,3-dimethyl ester → Dimethyl 5-morpholinoisophthalate
78% 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 | 1,3-Benzenedicarboxylic acid, 5-bromo-, 1,3-dimethyl ester | C₁₀H₉BrO₄ | |
| Reactant | Morpholine | C₄H₉NO | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | Dimethyl 5-morpholinoisophthalate | C₁₄H₁₇NO₅ | 78.22% |
Conditions
- Temperature
- 100 °C
Yield
- 78% of Dimethyl 5-morpholinoisophthalate.
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.
- 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%
- 2-Cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide13%
Procedure
Copied from the source record, unedited
To a solution of dimethyl 5-bromoisophthalate (10 g, 36.62 mmol) in toluene (100 mL) where BINAP (2.5 g, 4.01 mmol), morpholine (4.4 g, 50.50 mmol), CESIUM CARBONATE (18 g, 55.25 mmol) and PALLADIUM(II) ACETATE (0.9 g, 4.01 mmol) added. The solution was heated to reflux under inert atm for 14h. The silvent was filtered and the filtrate was concentrated. The residue was purified by column chropmatography (Hep:EA) 1:1 to give dimethyl 5-morpholinoisophthalate (8.00 g, 78 %)
The source
This record comes from experimental reaction archive (ord-ff0eb93bbb4b45cdb3807c4588dd206f). Open the source and check it against what is on this page.
experimental reaction archive record ord-ff0eb93bbb4b45cdb3807c4588dd206f 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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