Iodine → (4-Fluoro-3-phenoxyphenyl)-boronic acid

HRID 1458389Notes

Reaction equation

HRID 1458389 reaction equation
[C:1]1([O:7][C:8]2[CH:13]=[C:12](Br)[CH:11]=[CH:10][C:9]=2[F:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Mg].II.[B:19](OC)([O:22]C)[O:20]C>O1CCCC1.BrCCBr.C(OCC)C.C(O)(=O)C.O>[F:15][C:9]1[CH:10]=[CH:11][C:12]([B:19]([OH:22])[OH:20])=[CH:13][C:8]=1[O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 4

HCID 807IodineHCID 8470Trimethyl borateHCID 5462224MagnesiumHCID 11076399Benzene, 4-bromo-1-fluoro-2-phenoxy-

Product 1

HCID 21185404(4-Fluoro-3-phenoxyphenyl)-boronic acidYield 82%

Reagents, catalysts & solvents 5

HCID 78391,2-DibromoethaneCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-bromo-2-fluorophenyl phenyl ether (8.01 g, 30 mmol) in tetrahydrofuran is added dropwise over 30 minutes to a mixture of magnesium turnings (0.0802 g, 33 mmol), a crystal of iodine and a few drops of 1,2-dibromoethane in tetrahydrofuran at 50°-55° C. under nitrogen. After the addition is complete, the reaction mixture is stirred at 50°-55° C. for 70 minutes and cooled to room temperature. The cooled mixture is added over 25 minutes to a solution of trimethyl borate (4.09 mL, 36 mmol) in diethyl ether at dry ice/acetone bath temperature. After the addition is complete, the mixture is stirred at dry ice/acetone bath temperature for 20 minutes, allowed to warm to -10° C. over 25 minutes, diluted sequentially with acetic acid and water, stirred at room temperature for 30 minutes, and extracted with ether. The organic extract is washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a residue. A mixture of the residue in water is heated over a steam bath for 30 minutes, cooled to room temperature and filtered to obtain a solid which is washed with hexanes and dried to give the title product as a colorless solid (5.7 g, mp 177°-180° C., 82% yield)

Workup

  1. customat 50°-55° C.
  2. additionAfter the addition
  3. additionAfter the addition
  4. stirringthe mixture is stirred at dry ice/acetone bath temperature for 20 minutes
  5. temperatureto warm to -10° C. over 25 minutes
  6. stirringstirred at room temperature for 30 minutes
  7. extractionextracted with ether
  8. extractionThe organic extract
  9. washis washed with water
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customto obtain a residue
  13. temperatureis heated over a steam bath for 30 minutes
  14. temperaturecooled to room temperature
  15. filtrationfiltered
  16. customto obtain a solid which
  17. washis washed with hexanes
  18. customdried

Sources & evidence

ORD record
ord-1fd5000ff3d94deeac66493ba05b23d0
Source dataset
uspto-grants-1998_12
Patent number
US05849958

Reaction notes

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