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 (150 mg, 0.65 mmol) in dioxane (4 mL) was added (2R,6S)-2,6-dimethylpiperazine (221 mg, 1.94 mmol) followed by cesium carbonate (316 mg, 0.97 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (56.4 mg, 0.09 mmol) and diacetoxypalladium (14.51 mg, 0.06 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/ Methanol + 0.2% Et3N 100/0 =>90/10 over 20 min. The pure fractions was collected and concentrated to give (3R,5S)-1-(4-methoxy-3-nitrophenyl)-3,5-dimethylpiperazine (96 mg, 56.0 %) as red solid.
Sources & evidence
- ORD record
- ord-fb5c3a40f09e4b5fab2cf5db4493aed4
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Reaction notes
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