Pentamethyldiethylenetriamine → (4-Bromo-1-trityl-1H-imidazol-2-yl)-(5-ethyl-2-fluoro-biphenyl-3-yl)-methanol

HRID 2105033Notes

Reaction equation

HRID 2105033 reaction equation
[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([F:15])=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:8]=1)[CH3:2].CN(CCN(CCN(C)C)C)C.[Li]CCCC.[Br:33][C:34]1[N:35]=[C:36]([CH:58]=[O:59])[N:37]([C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:38]=1>C1COCC1>[Br:33][C:34]1[N:35]=[C:36]([CH:58]([C:5]2[C:6]([F:15])=[C:7]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:8]=[C:3]([CH2:1][CH3:2])[CH:4]=2)[OH:59])[N:37]([C:39]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:38]=1

Participants

6

Reactant 4

HCID 18196PentamethyldiethylenetriamineHCID 214329185-Ethyl-2-fluoro-biphenylHCID 862472204-bromo-1-trityl-1H-imidazole-2-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 68815883(4-Bromo-1-trityl-1H-imidazol-2-yl)-(5-ethyl-2-fluoro-biphenyl-3-yl)-methanolYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of Intermediate 228.2 (85 mg, 0.424 mmol) and PMDTA (0.10 mL, 0.478 mmol) in 4 ml THF at −78° C., was added BuLi (1.4 M in hexanes, 0.334 mL, 0.467 mmol). The mixture was stirred with warming to −40° C. over 30 min, recooled to −78° C., then a solution of Intermediate 175.1 (177 mg, 0.424 mmol) in 1.5 mL THF was added. The mixture was warmed to rt over 0.5 h. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with H2O (2×) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient) to afford 194 mg of Intermediate 228.3 as a colorless solid.

Workup

  1. customrecooled to −78° C.
  2. temperatureThe mixture was warmed to rt over 0.5 h
  3. customThe reaction was quenched with sat. NH4Cl
  4. additionwas diluted with EtOAc
  5. washThe organic phase was washed with H2O (2×) and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-a0779b89c9ca47c8a9d928895df38138
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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