Bromide ion → 4-Bromobiphenyl

HRID 398320Notes

Reaction equation

HRID 398320 reaction equation
II.[Br-:3].COC(=O)[C@@H]1CCCN1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH4+].[Cl-]>C1COCC1.CCOCC>[Br:3][C:13]1[CH:18]=[CH:17][C:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 259Bromide ionHCID 807IodineHCID 25517Ammonium ChlorideHCID 11106861HCID 11106861, compound

Product 1

HCID 71014-Bromobiphenyl

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
70 °C

Procedure

A solution of 4-bromobiphenyl (7.42 g, 31.87 mmol) in 40 mL THF was prepared, and 10 mL was added to Mg (0.85 g, 35.05 mmol) and one crystal of 12 in THF (10 mL). The Grignard reaction was initiated with the aid of gentle warming by a heat gun. After the iodine color had dissipated, the remaining 30 mL of bromide solution was added dropwise to the reaction mixture. After the reflux subsided, the solution was warmed over an oil bath (70° C.) for 30 minutes, then cooled to 0° C. N-benzyl-(S)-proline methyl ester (5, 2.18 g, 9.96 mmol) in THF (10 mL) was added. After the addition, the solution was allowed to warm to room temperature and stirred for another 8 hours. Saturated NH4Cl (150 mL) was added and the resulting mixture was diluted with Et2O (200 mL). The phases were separated and the organic phase was washed with H2O and brine, dried (MgSO4), and concentrated. The residue was purified over a short silica gel column using 5 to 20% EtOAc/pet ether to a give a white solid, which was recrystalized with CH2Cl2/pet ether to obtain white needles (4.106 g, 83%): mp 85-86° C., 1H NMR (300 MHz, CDCl3) δ 1.60-1.74 (m, 2 H), 1.76-1.88 (m, 1 H), 1.94-2.08 (m, 1 H), 2.40 (dd, J=16.6, 9.0 Hz, 1 H), 2.92-3.00 (m, 1 H), 3.10 (d, J=12.7 Hz, 1 H), 3.38 (d, J=12.5 Hz, 1 H), 4.06 (dd, J=9.3, 4.6 Hz, 1 H), 5.04 (s, 1 H), 7.04-7.60 (m, 14H), 7,68 (d, J=8.3 Hz, 2 H), 7.82 (d, J=8.3 Hz, 2 H).

Workup

  1. customThe Grignard reaction
  2. temperatureof gentle warming by a heat gun
  3. temperaturecooled to 0° C
  4. additionAfter the addition
  5. temperatureto warm to room temperature
  6. customThe phases were separated
  7. washthe organic phase was washed with H2O and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe residue was purified over a short silica gel column
  11. customa give a white solid, which
  12. customwas recrystalized with CH2Cl2/pet ether

Sources & evidence

ORD record
ord-379dd9dcd9c34bbc92e1208d425590aa
Source dataset
uspto-grants-2003_08
Patent number
US06610889B2

Reaction notes

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