Benzene, 1-bromo-3-ethyl- → (4-bromo-1-trityl-1H-imidazol-2-yl)(3-ethylphenyl)methanol

HRID 2105001Notes

Reaction equation

HRID 2105001 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH3:9])[CH:3]=1.[Li]CCCC.[Br:15][C:16]1[N:17]=[C:18]([CH:40]=[O:41])[N:19]([C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1>C1COCC1>[Br:15][C:16]1[N:17]=[C:18]([CH:40]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH3:9])[CH:3]=2)[OH:41])[N:19]([C:21]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:20]=1

Participants

5

Reactant 3

HCID 123170Benzene, 1-bromo-3-ethyl-HCID 862472204-bromo-1-trityl-1H-imidazole-2-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 68813719(4-bromo-1-trityl-1H-imidazol-2-yl)(3-ethylphenyl)methanolYield 77.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-bromo-3-ethylbenzene (266 mg, 1.44 mmol) in 7 mL THF at −78° C., was added BuLi (1.6 M in hexanes, 0.99 mL, 1.58 mmol). The mixture was stirred at −78° C. for 10 min, then a solution of Intermediate 175.1 (600 mg, 1.44 mmol) in 3 mL THF was added. The mixture was stirred at −78° C. for 1 h, then was removed from the cooling bath and stirred 20 min. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) to afford 585 mg of Intermediate 175.2 as a colorless solid. LCMS (4 min gradient, 50 to 100% B, A=95% H2O/5% CH3CN/0.1% TFA, B=95% CH3CN/5% H2O/0.1% TFA) RT=3.65 min, 523.10 (M+H)+.

Workup

  1. stirringThe mixture was stirred at −78° C. for 1 h
  2. customwas removed from the cooling bath
  3. stirringstirred 20 min
  4. customThe reaction was quenched with sat. NH4Cl
  5. additionwas diluted with EtOAc
  6. washThe organic phase was washed with H2O and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-f2c579b8fb8b4835a914f97e820afc9a
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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