4-Bromo-2-nitroanisole → cis-3,5-Dimethyl-1-[4-(methyloxy)-3-nitrophenyl]piperazine
Reaction equation
COc1ccc(Br)cc1[N+](=O)[O-].C[C@@H]1CNC[C@H](C)N1>C1COCCO1.CC(=O)O.CC(=O)O.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)cc1[N+](=O)[O-]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
To a solution of 4-bromo-1-methoxy-2-nitrobenzene (1500 mg, 6.46 mmol) in dioxane (40 mL) was added (2R,6S)-2,6-dimethylpiperazine (2215 mg, 19.39 mmol) followed by cesium carbonate (3159 mg, 9.70 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (564 mg, 0.91 mmol) and diacetoxypalladium (145 mg, 0.65 mmol). The resulting mixture was heated at 100 °C under argon over night (black). LCMS Ok. The solids were filtered through celite and washed with ethyl acetate. The ethyl acetate was evaporated under reduced pressure and the crude product was purified by flash- chromatograpy eluated with Dichloromethane/ 2 M NH3 in Methanol 100/0 =>80/20 over 20 min. The pure fractions was collected and concentrated to give (3R,5S)-1-(4-methoxy-3-nitrophenyl)-3,5-dimethylpiperazine (1540 mg, 90 %) as red solid.
Sources & evidence
- ORD record
- ord-5dbc6ee86ad94d33b87d1fb77112c522
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Reaction notes
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