4-phenyl-1-(triphenylmethyl)-1H-imidazole → (3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl) (4-phenyl-1-trityl-1H-imidazol-2-yl)methanol

HRID 2105087Notes

Reaction equation

HRID 2105087 reaction equation
[C:1]1([C:7]2[N:8]=[CH:9][N:10]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[Si:36]([O:43][C:44]1[C:45]([F:54])=[C:46]([CH:49]=[C:50]([CH2:52][CH3:53])[CH:51]=1)[CH:47]=[O:48])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37]>C1COCC1>[Si:36]([O:43][C:44]1[C:45]([F:54])=[C:46]([CH:47]([C:9]2[N:10]([C:12]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:11]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=2)[OH:48])[CH:49]=[C:50]([CH2:52][CH3:53])[CH:51]=1)([C:39]([CH3:40])([CH3:42])[CH3:41])([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 102217694-phenyl-1-(triphenylmethyl)-1H-imidazoleHCID 598380723-{[tert-Butyl(dimethyl)silyl]oxy}-5-ethyl-2-fluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 69125238(3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl) (4-phenyl-1-trityl-1H-imidazol-2-yl)methanolYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-phenyl-1-trityl-1H-imidazole (8.1) (1.37 g, 3.54 mmol) in 20 mL THF at 0° C., was added BuLi (1.6 M in hexanes, 2.66 mL, 4.25 mmol). The mixture was stirred at 0° C. for 30 min, then a solution of 3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorobenzaldehyde (188.3) (1.00 g, 3.54 mmol) in 3 mL THF was added dropwise. The mixture was stirred at 0° C. for 5 min, was removed from the cooling bath and stirred 45 min, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, 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 1.75 g of Intermediate 448.1 as a white foam. LCMS (2 min gradient) RT=2.22 min, 669.28 (M+H)+.

Workup

  1. stirringThe mixture was stirred at 0° C. for 5 min
  2. customwas removed from the cooling bath
  3. stirringstirred 45 min
  4. customwas quenched with sat. NH4Cl
  5. additionThe mixture was diluted with EtOAc
  6. washwashed 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-ae2ef370494b4f10a973496c52d0cf37
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

Loading…