Pyridine → 1-Bromo-4-[4-(trifluoromethoxy)phenoxy]benzene

HRID 1908993Notes

Reaction equation

HRID 1908993 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1.[Br:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 78084-BromophenolHCID 81531DiisopropylethylamineHCID 27343864-(Trifluoromethoxy)phenylboronic acid

Product 1

HCID 115300651-Bromo-4-[4-(trifluoromethoxy)phenoxy]benzeneYield 63%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(trifluoromethoxy)phenylboronic acid (10.0 g, 48.6 mmol) and 4-bromophenol (4.20 g, 24.3 mmol) in dichloromethane (250 ml) over 4 A molecular sieves was added copper (II) acetate (4.41 g, 24.3 mmol), diisopropylethylamine (21 ml, 121 mmol) and pyridine (10 ml, 121 mmol). The reaction mixture was stirred 12 hours at room temperature under positive pressure of dry air and concentrated in vacuo. The resulting residue was resuspended in ethyl acetate and 0.5 M HCl. The organic layer was extracted with water and brine, dried over magnesium sulfate and concentrated in vacuo. Purification by silica gel chromatography (ethyl acetate/hexanes) provided 5.07 g 1-bromo-4-(4-(trifluoromethoxy)phenoxy)benzene (63% yield) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=9.3 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H), 6.99 (d, J=9.3 Hz, 1H), 6.89 (d, J=8.9 Hz, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. extractionThe organic layer was extracted with water and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8a7ad4af3107422faed04214307cb453
Source dataset
uspto-grants-2013_12
Patent number
US08598354B2

Reaction notes

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