Buchwald–Hartwig amination: Methyl 3-bromo-5-nitrobenzoate → Methyl 3-(4-methyl-1-piperazinyl)-5-nitrobenzoate
65% yield, run at 110 °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 | Methyl 3-bromo-5-nitrobenzoate | C₈H₆BrNO₄ | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | Methyl 3-(4-methyl-1-piperazinyl)-5-nitrobenzoate | C₁₃H₁₇N₃O₄ | 65.18% |
Conditions
- Temperature
- 110 °C
Yield
- 65% of Methyl 3-(4-methyl-1-piperazinyl)-5-nitrobenzoate.
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.
- N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide80%
- Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate64%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine64%
- 4-(4-Methyl-1-piperazinyl)phenol51%
- 1-(5-Bromopyridin-3-yl)-4-methylpiperazine21%
- 1-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)-4-methylpiperazine0%
- Ethyl 4-[(2,4-dichlorophenyl)amino]-7-methoxy-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate0%
- Ethyl 4-[(2,4-difluorophenyl)amino]-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate0%
- N-[5-(1H-imidazol-2-yl)-2-methylphenyl]-4-[[3-(4-methylpiperazin-1-yl)-2-pyridinyl]methoxy]benzamide0%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine0%
Procedure
Copied from the source record, unedited
To the stirred suspension ofmethyl 3-bromo-5-nitrobenzoate (2 g, 7.69 mmol) , cesium carbonate (12.53 g, 38.46 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.111 g, 0.19 mmol) in Dioxane (12 mL) (degassed with N2) was added pd (dba)3 (0.176 g, 0.19 mmol) and cesium carbonate (12.53 g, 38.46 mmol) AND rxn was heated at 110 ºC for 1 hr in microwaved. LCMS showed the m+1= 280. The crude raection mixture was filtered over celite. The filtrate was concentarted. The crude solid was diluted by 20 mL ethyl acetate, washed with 3x10 mL water, brine, collected the organic layers, concentrated. The crude solid was added to a silica gel column and was eluted with 0-10% methanol in DCM. Collected desired fractions. Obtained=1.4 gm. 1H NMR (300 MHz, DICHLOROMETHANE- _d_ 2) d
The source
This record comes from experimental reaction archive (ord-0986b91ec7734959810ebeac46571d3f). Open the source and check it against what is on this page.
experimental reaction archive record ord-0986b91ec7734959810ebeac46571d3f 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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