3-{[tert-Butyl(dimethyl)silyl]oxy}-5-ethyl-2-fluorobenzaldehyde → (3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(5,6-dimethyl-1-trityl-1H-benzo[d]imidazol-2-yl)methanol

HRID 2105079Notes

Reaction equation

HRID 2105079 reaction equation
[CH3:1][C:2]1[C:29]([CH3:30])=[CH:28][C:5]2[N:6]([C:9]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=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:7]2[N:6]([C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:5]3[CH:28]=[C:29]([CH3:30])[C:2]([CH3:1])=[CH:3][C:4]=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 598380723-{[tert-Butyl(dimethyl)silyl]oxy}-5-ethyl-2-fluorobenzaldehydeHCID 688140645,6-dimethyl-1-trityl-1H-benzo[d]imidazoleHCID 178418339Butyllithium

Product 1

HCID 68812924(3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(5,6-dimethyl-1-trityl-1H-benzo[d]imidazol-2-yl)methanolYield 66.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of intermediate 415.1 (100 mg, 0.257 mmol) in 2 mL THF at 0° C., was added BuLi (1.6 M in hexanes, 193 μL, 0.309 mmol). The mixture was stirred at 0° C. for 20 min, then a solution of 3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorobenzaldehyde (188.3) (72.6 mg, 0.257 mmol) in 0.6 mL THF was added. The mixture was removed from the ice bath and stirred 70 min, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) to afford 115 mg of intermediate 415.2. LCMS (2 min gradient) RT=2.24 min, 671.13 (M+H)+.

Workup

  1. customThe mixture was removed from the ice bath
  2. stirringstirred 70 min
  3. customwas quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-3b9fc0fa410c4e249a1d38f0b5214067
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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