1-Bromo-4-iodobenzene → 1-(4-Bromophenyl)-cis-3,5-dimethylpiperazine

HRID 2281730Notes

Reaction equation

HRID 2281730 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.C1C=CC2C(C3C(O)=CC=C4C=3C=CC=C4)=C(O)C=CC=2C=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:39][C@H:40]1[CH2:45][NH:44][CH2:43][C@@H:42]([CH3:46])[NH:41]1>CCOC(C)=O.[Cu]I.CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:44]2[CH2:43][C@H:42]([CH3:46])[NH:41][C@H:40]([CH3:39])[CH2:45]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 115221-Bromo-4-iodobenzeneHCID 11762BinolHCID 62657Potassium Phosphate, TribasicHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 667303611-(4-Bromophenyl)-cis-3,5-dimethylpiperazineYield 60.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A microwave vial was charged with 1-bromo-4-iodobenzene (1.0 g, 3.5 mmol), CuI (0.135 g, 0.707 mmol), BINOL (0.202 g, 0.707 mmol), and K3PO4 (1.5 g. 7.1 mmol). The vial was capped and then evacuated and backfilled with Ar. Cis-2,6-dimethylpiperazine (0.605 g, 5.30 mmol) and DMF (4 mL) were then added. The resulting mixture was stirred at rt for 4 d. The mixture was diluted with EtOAc, filtered through a cake of Celite and the filtrate was concentrated to give the crude product. Crude product was purified by flash chromatography using MeOH/CH2Cl2 (2:98 to 15:85) to give the title compound as a red solid (567 mg, 59%). 1H NMR (400 MHz, MeOD) δ 7.33 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 3.63-3.60 (m, 2H), 3.18-3.07 (m, 2H), 2.40 (t, J=11.6 Hz, 2H), 1.23 (d, J=6.4 Hz, 6H); MS ESI 269.0 [M+H]+, calcd for [C12H17BrN2+H]+ 269.06.

Workup

  1. customThe vial was capped
  2. customevacuated
  3. filtrationfiltered through a cake of Celite
  4. concentrationthe filtrate was concentrated
  5. customto give the crude product
  6. customCrude product was purified by flash chromatography

Sources & evidence

ORD record
ord-41866a0377ec495c9657ef70c2d871c6
Source dataset
uspto-grants-2015_09
Patent number
US09139563B2

Reaction notes

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