Ammonium Chloride → (3-(tert-butyldimethylsilyloxy)-5-ethoxy-2-fluorophenyl)(4-phenyl-1-trityl-1H-imidazol-2-yl)methanol

HRID 2104986Notes

Reaction equation

HRID 2104986 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:55])=[C:46]([CH:49]=[C:50]([O:52][CH2:53][CH3:54])[CH:51]=1)[CH:47]=[O:48])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Si:36]([O:43][C:44]1[C:45]([F:55])=[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]([O:52][CH2:53][CH3:54])[CH:51]=1)([C:39]([CH3:40])([CH3:42])[CH3:41])([CH3:38])[CH3:37]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 102217694-phenyl-1-(triphenylmethyl)-1H-imidazoleHCID 180033743-(Tert-butyldimethylsilyloxy)-5-ethoxy-2-fluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 68815621(3-(tert-butyldimethylsilyloxy)-5-ethoxy-2-fluorophenyl)(4-phenyl-1-trityl-1H-imidazol-2-yl)methanolYield 84.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of intermediate 8.1 (1.00 g, 2.59 mmol) in 20 mL THF at 0° C., was added BuLi (1.4 M, 2.03 mL, 2.85 mmol). The mixture was stirred for 30 min at 0° C., then a solution of 3-(tert-butyldimethylsilyloxy)-5-ethoxy-2-fluorobenzaldehyde (773 mg, 2.59 mmol) in 2 mL THF was added dropwise. The mixture was stirred at 0° C. for 30 min, quenced with sat. NH4Cl and 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 30% EtOAc/hexanes, gradient) to afford 1.50 g (80%) of Intermediate 123.1 as a pale yellow solid.

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 min
  2. washThe organic phase was washed with H2O and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes, gradient)

Sources & evidence

ORD record
ord-33e523b48bc341408359c5bce1fb9eec
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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